Viral inhibitors

ABSTRACT

The present invention relates to a pharmaceutical composition for the treatment or prevention of viral infections comprising as an active principle at least one imidazo[4,5-c]pyridine derivative having the general formula (Z): (formula). The invention also relates to processes for the preparation of compounds according to the invention having above mentioned general formula and their use as a medicine or to treat or prevent viral infections.

FIELD OF THE INVENTION

The present invention relates to a series of novelimidazo[4,5-c]pyridine derivatives, processes for their preparation,their use to treat or prevent viral infections and their use tomanufacture a medicine to treat or prevent viral infections,particularly infections with viruses belonging to the family of theFlaviviridae and Picornaviridae and more preferably infections withhepatitis-C-virus (HCV). The present invention also relates to the useof novel imidazo[4,5-c]pyridine derivatives to treat viral infectionsand their use to manufacture a medicine to treat viral infections,preferably infections with viruses belonging to the family of theFlaviviridae or Picornaviridae and more particularly infections withBVDV, HCV or Coxsackie viruses.

BACKGROUND OF THE INVENTION

The family of the Flaviviridae consists of 3 genera, the pestiviruses,the flaviviruses and the hepaciviruses and also contains the hepatitis Gvirus (HGV/GBV-C) that has not yet been assigned to a genus.Pestiviruses such as the Classical Swine Fever Virus (CSFV), the BovineViral Diarrhea Virus (BVDV) and the Border Disease Virus (BDV) causeinfections of domestic livestock (respectively pigs, cattle and sheep)and are responsible for significant economic losses world-wide. BVDV,the prototypic representative of the pestivirus genus is ubiquitous andcauses a range of clinical manifestations, including abortion,teratogenesis, respiratory problems, chronic wasting disease, immunesystem dysfunction, and predisposition to secondary viral and bacterialinfections and may also cause acute fatal disease. Foetuses of cattlecan be infected persistently with BVDV, these animals remain viremicthroughout life and serve as a continuous sources for virus spread inherds.

Vaccines are used in some countries with varying degrees of success tocontrol pestivirus disease. In other countries, animal culling andslaughter are used to contain pestivirus disease outbreaks.

The World Health Organization estimates that world-wide 170 millionpeople (3% of the world's population) are chronically infected with HCV.These chronic carriers are at risk of developing cirrhosis and/or livercancer. In studies with a 10 to 20 year follow-up, cirrhosis developedin 20-30% of the patients, 1 to 5% of whom may develop liver cancerduring the next then years. The only treatment option available today isthe use of interferon α-2 (or its pegylated from) either alone orcombined with ribavirin. However, sustained response is only observed inabout 40% of the patients and treatment is associated with seriousadverse effects. There is thus an urgent need for potent and selectiveinhibitors of the replication of the HCV in order to treat infectionswith HCV. Furthermore, the study of specific inhibitors of HCVreplication has been hampered by the fact that it is not possible topropagate HCV (efficiently) in cell culture. Since HCV and pestivirusesbelong to the same virus family and share many similarities(organisation of the genome, analogous gene products and replicationcycle), pestiviruses have been adopted as a model and surrogate for HCV.For example BVDV is closely related to hepatitis C virus (HCV) and usedas a surrogate virus in drug development for HCV infection.

The compound3-[((2-dipropylamino)ethyl)thio]-5H-1,2,4-triazino[5,6-b]indole has beenreported to selectively inhibit the replication of BVDV and otherpestiviruses (Baginski S G et al., Proc. Natl. Acad. Sci. U.S.A. 2000Jul. 5;97(14):7981-6). Currently, there is no treatment strategyavailable for controlling infections caused by pestiviruses.

Coxsackie viruses belong to the group of the enteroviruses, family ofthe Picornaviridae. They cause a heterogeneous group of infectionsincluding herpangina, aseptic meningitis, a common-cold-like syndrome, anon-paralytic poliomyelitis-like syndrome, epidemic pleurodynia (anacute, febrile, infectious disease generally occurring in epidemics),hand-foot-mouth syndrome, pediatric and adult pancreatitis and seriousmyocarditis.

Currently only pleconaril(3-13,5-dimethyl-4-[[3-methyl-5-isoxazolyl)propyl)phenyl]-5-(trifluoromethyl-1,2,4-oxadiazole))and enviroxime (2-amino-1-(isopropylsulfonyl)-6-benzimidazole phenylketone oxime) have been studied clinically for the treatment ofinfections with enteroviruses. Pleconaril is a so called “capsidfunction-inhibitor”; enviroxime prevents the formation of the RNAreplicative intermediate. Enviroxime resulted in only modest clinicaland virological benefit in some studies and no benefits in others.Clinical response with pleconaril has been observed in some studies, butthe compound has not been approved by the Food and Drug Administration(hearing of Mar. 18^(th), 2002).

U.S. Pat. Nos. 4,914,108, 4,990,518, 4,988,707, 5,227,384, 5.302,601 and5,486,525 describe 5-substituted [4,5-c]imidazopyridine derivativesuseful in the treatment of diseases or disorders mediated byplatelet-activating factor. The compounds were found to inhibit ³H-PAFbinding to human platelets.

EP 1132381 describes esters of 2,2-dimethylpropionic acid comprising abenzmidazole structure having an inhibitory activity of elastase.

WO 96/1192 describes compounds of the general formula Ar1-Q-Ar2-YR-Z,wherein Z is optionally a [4,5-c]imidazopyridine which are proposed asLTA4 hydrolase inhibitors useful for the treatment of inflammatorydiseases mediated by LTB₄ production

WO 96112703 describes heteroarylthioalkyl thiophenolic compounds having5-lipoxygenase inhibitory activity which are suggested to be useful inthe treatment of 5-lipoxygenase mediated conditions.

Chemical Abstracts acc no. 1987:18435 and Chemical Abstracts acc no.1983:594812 describe the synthesis of two imidazo[4,5-b] and ofimidazo[4,5c]pyridine derivatives substituted with piperazinyl andfuranyl groups.

EP 1162196 describes fused ring compounds for the use as therapeuticagents for hepatitis C. The fused 5 and 6 membered ring is made up ofoptionally substituted carbon atoms or nitrogen atoms and optionally oneoxygen, sulfur atom or substituted nitrogen atom on the 5 membered ring.WO 95/02597 describes imidazo[4,5c]pyridine derivatives not substitutedat the N5 with antiviral activity

GB2158440 describes 4,5,6,7-tetrahydroimidazo[4,5-c]pyridine derivativeswith antiviral activities.

STN database accession 110:165603 & Khimiko-Farmatsevtichsskii Zurnal.23:1, (1989), 26-59, describe spinaceamine derivatives such as5H-imidazo [4,5-c]pyridine-5-ethanol,1,4,6,7-tetrahydro-alpha-(4methoxyphenyl)-1,2-dimethyl compounds withantiviral activity (small pox virus).

STN database accession 132:222537 and HU73019 describe N-alkylatedazoles with antibacterial activity.

WO9927929 describes [4.3.0] nitrogen containing ring systems andhomolozous compounds which are proposed as farnesyl-protein transferaseinhibitors applicable in the treatment of cancer.

WO9611192 describes 5-substituted imidazo(4,5)pyridine compounds andrelated molecules for use as anti-inflammatory compounds by inhibitingleukotriene A4 hydrolase.

EP344414 describes 5-Substituted imidazo[4.5-c]pyridines for thetreatment of diseases such as inflammation, cardiovascular disorders andasthma.

WO9516687 describes imidazopyridine indoles which act as plateletactivating factor antagonists:

J. Comb. Chem. (2000) 4:5, 475-483 describes the synthesis ofbenzimidazole compound for use in small organic libraries.

In view of their important pharmacological value, there is a need fordrugs having antiviral activity, optionally selective activity againstviruses belonging to the family of Flaviviridae including hepatitis Cvirus, and against viruses belong to the family of Picornaviridae.

SUMMARY OF THE INVENTION

In the present invention, new selective anti-viral compounds are beingprovided. The compounds are imidazo[4,5-c]pyridine derivatives and ithas been shown that they possess a broad anti-viral activity. Members ofthe Flaviviridae and of the Picornaviridae families are being inhibited.The present invention demons that the compounds inhibit the replicationof BVDV, HCV and Coxsackie virus. Furthermore, the anti-BVDV activity ofthe compounds is based on the inhibition of the viral polymerase enzymeof BVDV. Therefore, these imidazo[4,5-c]pyridine derivatives constitutea new potent class of anti-viral compounds that can be used in thetreatment and prevention of viral infections in animals, mammals andhumans, more specifically for the treatment and prevention of BVDV, HCVand Coxsackie virus infections.

The present invention relates to imidazo[4,5-c]pyridine derivatives. Theinvention further relates to compounds having anti-viral activity, morespecifically to imidazo[4,5-c]pyridine derivatives that inhibit thereplication of viruses. Most particularly, the invention relates toimidazo[4,5-c]pyridine derivatives which inhibit the replication ofviruses of the family of the Flaviviridae and the Picornaviridae and yetmore specifically to compounds that inhibit the replication of BVDV(Bovine Viral Diarrhea Virus), HCV (Hepatitis C Virus) and Coxsackievirus. Present invention furthermore relates to the use of the compoundsas a medicine and more specifically to use the compounds as ananti-viral. The invention also relates to methods for preparation of allsuch compounds and pharmaceutical compositions comprising them. Theinvention further relates to the use of said compounds in themanufacture of a medicament useful for the treatment of BVDV, HCV orCoxsackie virus infections, as well as for treatment of other viral,retroviral or lentiviral infections such as HIV. The present inventionalso relates to a method of treatment of viral infections, by using saidcompounds.

One aspect of the present invention is the provision ofimidazo[4,5-c]pyridine derivatives, compounds of formula (A) whicheffectively show antiviral properties, in particular against members ofthe Flaviviridae and the Picornaviridae and more in particular againstBVDV, HCV and Coxsackie virus, and consequently may be useful for thetreatment of subjects infected with BVDV, HCV or Coxsackie virus.

According to a first aspect the invention relates to the use ofimidazo[4,5-c]pyridine compounds as antiviral compounds, moreparticularly as compounds active against BVDV, HCV and Coxsackivirus,which correspond to the general formula (Z),

wherein:

-   -   the dotted lines represent an optional double bond, provided        that no two double bonds are adjacent to one another, and that        the dotted lines represent at least 3, optionally 4 double        bonds;    -   R¹ is selected from hydrogen; aryl unsubstituted or substituted        with one or more R⁶, heterocyclic ring unsubstituted or        substituted with one or more R⁶, C₃₋₁₀ cycloalkyl unsubstituted        or substituted with one or more R⁶ and C₄₋₁₀ cycloalkenyl        unsubstituted or substituted with one or more R⁶;    -   Y is selected from the group consisting of a single bond, O;        S(O)_(m); NR¹¹; and a divalent, saturated or unsaturated,        substituted or unsubstituted C₁-C₁₀ hydrocarbon group optionally        including one or more heteroatoms in the main chain, said        heteroatoms being selected from the groups consisting of O, S,        and N; such as C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene,        —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—, —S—(CH₂)₁₋₅—,        —(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—, —(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄—        and C₃₋₁₀ cycloalkylidene;    -   Each R² and R⁴ is independently selected from the group        consisting of hydrogen C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂;        NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy;        arylthio; arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃10 cycloalkylthio; C₃₋₁₀ cycloalkylthio; C₃₋₁₀        cycloalkenyl; C₃₋₁₀ cycloalkynyl; 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; or, when one of R²⁵ or        R²⁶ is different from hydrogen, either R² or R⁴ is selected from        (═O), (═S), and (═NR²⁷);    -   X is selected from the group consisting of a divalent, saturated        or unsaturated, substituted or unsubstituted C₁-C₁₀ hydrocarbon        group optionally including one or more heteroatoms in the main        chain (provided that the heteroatom is not linked to N of the        nucleus), said heteroatoms being selected from the group        consisting of O, S, and N; such as C₁₋₆ alkylene, (for example        —CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂),        —(CH₂)₂₋₄—O—(CH₂)₂₋₄—, —(CH₂)₂₋₄—S—(CH₂)₂₋₄—,        —(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene        (such as —CH═CH—CH₂—), C₂₋₆ alkynylene;    -   m is any integer from 0 to 2;    -   R³ is selected from the group consisting of aryl; aryloxy;        arylthio; aryl-NR¹⁰—; 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring;; and each of said        aryl, aryloxy, arylthio, aryl-NR¹⁰—5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring is optionally        substituted with one or more R¹⁷; C₃₋₁₀ cycloalkyl,        oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenyl with the        proviso that the double bond cannot be adjacent to a nitrogen; H        with the proviso that if X is an alkylene, an alkenylene or an        alkynylene, then X comprises at least 5 carbon atoms;    -   R⁵ is independently selected from the group consisting of        hydrogen; C₁₋₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈        alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   Each R⁶ and R¹⁷ is independently selected from the group        consisting of hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸;        OCF₃; haloalkyl; C(═O)R¹⁸; C(═S)R¹⁸; SH; aryl; aryloxy;        arylthio; arylalkyl; arylalkyloxy (optionally a oxybenzyl);        arylalkylthio (optionally a benzylthio); 5 or 6 membered        heterocyclic, oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈        hydroxyalkyl; and each of said aryl, aryloxy, arylthio,        arylalkyl, arylalkyloxy (optionally a oxybenzyl), arylalkylthio        (optionally a benzylthio), 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl is        optionally substituted with 1 or more R¹⁹;    -   Each R⁷ and R⁸ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6 membered heterocyclic ring;        C(═O)R¹²; C(═S)R¹² ; an amino acid residue linked through a        carboxyl group thereof; alternatively, R⁷ and R⁸, together with        the nitrogen to which they are attached, combine to form a 5-6        membered heterocyclic ring;    -   Each R⁹ and R¹⁸ is independently selected from the group        consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl an        amino acid residue linked through an amino group thereof;    -   Each R¹⁰ and R¹¹ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl; C(═O)R¹²; 5-6 membered        heterocyclin ring; an amino acid residue linked through a        carboxyl group thereof;    -   R¹² is independently selected from the group consisting of H;        C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; an amino acid residue linked through an amino        group thereof;    -   Each R¹³ and R¹⁴ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═S)R¹²; an amino        acid residue linked through a carboxyl group thereof;    -   Each R¹⁵ and R¹⁶ is independently selected from the group        consisting of H; C₁₋₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; aryl;        C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid residue        linked through a carboxyl group thereof;    -   R¹⁹ is independently selected from the group consisting of H;        C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy, preferably C₁₋₆ alkoxy; C₁₋₈ alkylthio;        C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C₄₋₁₀ cycloalkynyl;        halogen; OH; CN; NO₂; NR²⁰R²¹; OCF₃; haloalkyl; C(═O)R²²;        C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆ alkyl); aryl;        aryloxy; arylthio; arylalkyl; and each of said aryl, aryloxy,        arylthio, arylalkyl substituted with 1 or more halogens,        particularly a phenyl substituted with 1-2 halogens;        hydroxyalkyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring each unsubstituted or substituted with 1        or more halogens;    -   Each R²⁰ and R²¹ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈        alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; C(═O)R¹², C(═S)R¹²;    -   R²² is independently selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈        alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴; aryl; C₃₋₁₀ cycloalkyl,; C₄₋₁₀        cycloalkenyl;    -   Each R²³ and R²⁴ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl, preferably C₂₋₃ alkyl,        wherein C₂₋₃ alkyl taken together with N of R²² can form a        saturated heterocycle, which heterocycle is optionally        substituted with OH or aryl or an amino acid residue;    -   Each R²⁵ or R²⁶, selected from the group consisting of of H,        C₁₋₁₈ alkyl, preferably C₁₋₄ alkyl; C₃₋₁₀ cycloalkyl, such as        C₅₋₁₀ bicycloalkyl; C₃₋₁₀ cycloalkenyl; (C₃₋₈ cycloalkyl)-C₁₋₃        alkyl; aryl, such as phenyl; 5 or 6 membered heterocyclic ring,        such as pyridyl; alkylaryl, such as benzyl; and each of said        C₁₋₁₈ alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl, C₅₋₁₀ bicycloalkyl,        adamantyl, phenyl, pyridyl and benzyl is optionally substituted        with 1-4 of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OH,        oxybenzyl, and OH; and heterocyclic ring having 3 to 7 carbon        atoms, preferably a saturated heterocyclic ring wherein the        heteroatoms are S, S(O), or S(O)₂ separated from the        imidazopyridyl ring nitrogen atom by at least 2 heterocyclic        ring carbon atoms. Provided that either R²⁵ or R²⁶ is hydrogen.        Typically R²⁵ or R²⁶ is cyclopentyl or cyclohexyl; provided that        if the compound is substituted at R²⁵ or R²⁶, either R² or R⁴ is        selected from (═O), (═S), and (═NR²⁷); and    -   R²⁷ is selected from the group consisting of H, C₁₋₁₈ alkyl,        C₃₋₁₀ cycloalkyl, (C₃₋₁₀ cycloalkyl)-C₁₋₆alkyl; aryl; arylalkyl,        such as benzyl.

According to a second aspect, the invention relates toimidazo[4,5-c]pyridine compounds, which according to the generalembodiment of the invention correspond to compounds according to thegeneral formula (A), pharmaceutically acceptable salts, solvates,tautomers, isomers thereof,

wherein:

-   -   the dotted lines represent an optional double bond, provided        that no two double bonds are adjacent to one another, and that        the dotted lines represent at least 3, optionally 4 double        bonds;    -   R¹ is selected from hydrogen; aryl unsubstituted or substituted        with one or more R⁶, heterocyclic ring unsubstituted or        substituted with one or more R⁶, C₃₋₁₀ cycloalkyl unsubstituted        or substituted with one or more R⁶ and C₄₋₁₀ cycloalkenyl        unsubstituted or substituted with one or more R⁶;    -   Y is selected from the group consisting of a single bond, O;        S(O)_(m); NR¹¹; and a divalent, saturated or unsaturated,        substituted or unsubstituted C₁-C₁₀ hydrocarbon group optionally        including one or more heteroatoms in the main chain, said        heteroatoms being selected from the groups consisting of O, S,        and N; such as C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene,        —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—, —S—(CH₂)₁₋₅—,        —CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—, —(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄—        and C₃₋₁₀ cycloalkylidene;    -   Each R² and R⁴ is independently selected from the group        consisting of hydrogen C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂;        NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(S)R⁹; SH; aryl; aryloxy;        arylthio; arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio; C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring; or, when one of R²⁵ or R²⁶ is different        from hydrogen, either R² or R⁴ is selected from (═O), (═S), and        (═NR²⁷);    -   X is selected from the group consisting of a divalent, saturated        or unsaturated, substituted or unsubstituted C₁-C₁₀ hydrocarbon        group optionally including one or more heteroatoms in the main        chain (provided that the heteroatom is not linked to N of the        nucleus), said heteroatoms being selected from the group        consisting of O, S, and N; such as C₁₋₆ alkylene, (for example        —CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂),        —(CH₂)₂₋₄—O—(CH₂)₂₋₄—, —(CH₂)₂₋₄—S—(CH₂)₂₋₄—,        —(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene        (such as —CH═CH—CH₂—), C₂₋₆ alkynylene;    -   m is any integer from 0 to 2;    -   R³ is selected from the group consisting of aryl; aryloxy;        arylthio; aryl-NR¹⁰—; 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; and each of said aryl,        aryloxy, arylthio, aryl-NR¹⁰—, 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring is optionally        substituted with one or more R¹⁷; C₃₋₁₀ cycloalkyl,        oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenyl with the        proviso that the double bond cannot be adjacent to a nitrogen; H        with the proviso that if X is an alkylene, an alkenylene or an        alkynylene, then X comprises at least 5 carbon atoms;    -   R⁵ is independently selected from the group consisting of        hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈        alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   Each R⁶ and R¹⁷ is independently selected from the group        consisting of hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸;        OCF₃; haloalkyl; C(═O)R¹⁸; C(═S)R¹⁸; SH; aryl; aryloxy;        arylthio; arylalkyl; arylalkyloxy (optionally a oxybenzyl);        arylalkylthio (optionally a benzylthio); 5 or 6 membered        heterocyclic, oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈        hydroxyalkyl; and each of said aryl, aryloxy, arylthio,        arylalkyl, arylalkyloxy (optionally a oxybenzyl), arylalkylthio        (optionally a benzylthio), 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl is        optionally substituted with 1 or more R¹⁹;    -   Each R⁷ and R⁸ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6 membered heterocyclic ring;        C(═O)R¹²; C(═S)R¹² ; an amino acid residue linked through a        carboxyl group thereof; alternatively, R⁷ and R⁸, together with        the nitrogen to which they are attached, combine to form a 5-6        membered heterocyclic ring;    -   Each R⁹ and R¹⁸ is independently selected from the group        consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl an        amino acid residue linked through an amino group thereof;    -   Each R¹⁰ and R¹¹ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl; C(═O)R¹²; 5-6 membered        heterocyclin ring; an amino acid residue linked through a        carboxyl group thereof;    -   R¹² is independently selected from the group consisting of H;        C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; an amino acid residue linked through an amino        group thereof;    -   Each R¹³ and R¹⁴ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═S)R¹²; an amino        acid residue linked through a carboxyl group thereof;    -   Each R¹⁵ and R¹⁶ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl;        aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid        residue linked through a carboxyl group thereof;    -   R¹⁹ is independently selected from the group consisting of H;        C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy, preferably C₁₋₆ alkoxy; C₁₋₁₈ alkylthio;        C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C₄₋₁₀ cycloalkynyl;        halogen; OH; CN; NO₂; NR²⁰R²¹; OCF₃; haloalkyl; C(═O)R²²;        C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆ alkyl); aryl;        aryloxy; arylthio; arylalkyl; and each of said aryl, aryloxy,        arylthio, arylalkyl substituted with 1 or more halogens,        particularly a phenyl substituted with 1-2 halogens;        hydroxyalkyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring each unsubstituted or substituted with 1        or more halogens;    -   Each R²⁰ and R²¹ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈        alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ C(═O)R¹²,        C(═S)R¹²;    -   R²² is independently selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈        alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴; aryl; C₃₋₁₀ cycloalkyl,; C₄₋₁₀        cycloalkenyl;    -   Each R²³ and R²⁴ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl, preferably C₂₋₃ alkyl,        wherein C₂₋₃ alkyl taken together with N of R²² can form a        saturated heterocycle, which heterocycle is optionally        substituted with OH or aryl or an amino acid residue;    -   Each R²⁵ or R²⁶, selected from the group consisting of of H,        C₁₋₁₈ alkyl, preferably C₁₋₄ alkyl; C₃₋₁₀ cycloalkyl, such as        C₅₋₁₀ bicycloalkyl; C₃₋₁₀ cycloalkenyl; (C₃₋₈ cycloalkyl)-C₁₋₃        alkyl; aryl, such as phenyl; 5 or 6 membered heterocyclic ring,        such as pyridyl; alkylaryl, such as benzyl; and each of said        C₁₋₁₈ alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl, C₅₋₁₀ bicycloalkyl,        adamantyl, phenyl, pyridyl and benzyl is optionally substituted        with 1-4 of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OH,        oxybenzyl, and OH; and heterocyclic ring having 3 to 7 carbon        atoms, preferably a saturated heterocyclic ring wherein the        heteroatoms are S, S(O), or S(O)₂ separated from the        imidazopyridyl ring nitrogen atom by at least 2 heterocyclic        ring carbon atoms. Provided that either R²⁵ or R²⁶ is hydrogen.        Typically R²⁵ or R²⁶ is cyclopentyl or cyclohexyl; provided that        if the compound is substituted at R²⁵ or R²⁶, either R² or R⁴ is        selected from (═O), (═S), and (═NR²⁷); and    -   R²⁷ is selected from the group consisting of H, C₁₋₁₈ alkyl,        C₃₋₁₀ cycloalkyl, (C₃₋₁₀ cycloalkyl)-C₁₋₆ alkyl; aryl;        arylalkyl, such as benzyl.

More particularly, the present invention relates to compounds accordingto the general formula (Z) and/or (A) as defined above, provided that:

-   -   the substituents X, Y, R¹, R², R³, R⁴, R⁵ are not a        cephalosporin or wherein the substituents X, Y, R¹, R², R³, R⁴,        R⁵ are not an azabicyclo group, more particularly not        5-Thia-1-aza-bicyclo[4.2.0]oct-2-en-8-one;    -   the compound is not        5-(2-piperidin-1-yl-ethyl)-2-(4-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-5-ium        bromide (X=ethyl, Y=bond, R¹=phenyl substituted in para with OH,        R²═H, R³=unsubstituted heterocycle wherein heteroatom is N, R⁴,        R⁵═H) (as disclosed in example 52 of EP 1132381);    -   the compound is not        4-[5-(2-{4-[Bis-(4-fluorophenyl)-methyl]-piperazin-1-yl}-ethyl)-5H-imidazo[4,5-c]pyridin-2-yl]phenol        (X=ethyl, Y=bond, R¹=phenyl substituted in para with OH, R²═H,        R³=heterocycle with 2 N heteroatoms, wherein one N is        substituted with an arylalkyl consisting of CH(Phenyl)₂, wherein        each phenyl carries an F in para)(as disclosed in example 54 of        EP 1132381);    -   the compound is not        4-[5-{4-[Bis-(4-fluorophenyl)-methyl]-piperazin-1-yl}-propyl)-5H-imidazo[4,5-c]pyridin-2-yl]phenol        (X=butyl, Y=bond, R¹=phenyl substituted in para with OH, R²═H.        R³=heterocycle with 2 N heteroatoms, wherein one N is        substituted with an arylalkyl consisting of CH(Phenyl)₂, wherein        each phenyl carries an F in para)(as disclosed in example 55 of        EP 1132381);    -   The compound is not 5-(phenylmethyl)-5H-imidazo[4,5-c]pyridine        wherein phenyl is substituted with CONR¹⁵R¹⁶ and R¹⁵ is a        branched C3 alkyl and R¹⁶ is phenyl (X═—CH₂—; Y=bond;        R¹=hydrogen; R²═H; R³=phenyl substituted with 1 C(═O)R¹⁸,        wherein R¹⁸ is NR¹⁵R¹⁶, with R¹⁵ and R¹⁶ a branched C₆ alkyl;        R⁴═H) (as disclosed in example 35 of U.S. Pat. No. 5,302,601);    -   The compound is not        6-(5H-imidazo[4,5-c]pyridin-5-yl-methyl)-N-(1methylethyl)-N-phenyl-3-pyridinecarboxamide        (X═—CH₂—; Y=bond; R¹=hydrogen; R²═H, R³=pyridine substituted        with 1 R⁶, wherein R⁶=1 C=0 R¹⁸, wherein R¹⁸ is NR¹⁵R¹⁶, wherein        R¹⁵=isopropyl and R¹⁶=phenyl) (as disclosed in example 6 of U.S.        Pat. No. 4,990,518);    -   The compound is not a compound wherein X═—CH²—; Y=bond;        R¹=hydrogen; R²═H, R³=5-6 membered heterocyclic ring, in        particular a pyridinyl or furanyl, substituted with 1 R¹⁷        wherein R¹⁷═C(═O)R¹⁸, and wherein R¹⁸═NR¹⁵R¹⁶ and R¹⁵ and R¹⁶        are either a C₁₋₁₈ alkyl, in particular methyl, ethyl or        isopropyl, C₂₋₁₈ alkenyl, in particular 2-methyl allyl, or a        C₃₋₁₀ cycloalkyl, in particular cyclopentyl or cyclohexyl. (as        disclosed in U.S. Pat. No. 4,990,518);    -   The compound is not a compound wherein X═—CH²—; Y=bond;        R¹=hydrogen; R²═H, R³=5-6 membered heterocyclic ring, in        particular a pyridinyl or furanyl, substituted with 1 R¹⁷        wherein R¹⁷═C(═O)R¹⁸, and wherein R¹⁸═C₃₋₁₀cycloalkyl or C₄₋₁₀        cycloalkenyl.    -   The compound is not        2,6-bis(1,1,-dimethylethyl)-4-[[2-(5H-imidazo-[4,5-c]pyridin-5-yl)ethyl]thio]-phenol        hydrate and/or        2,6-bis(1,1,-dimethylethyl)-4-[[2-(5H-imidazo-[4,5-c]pyridin-5-yl)propyl]thio]-phenol        hydrate (X═CH²—CH²—; Y=bond; R¹=hydrogen, R²═H, R³=thioaryl        substituted with 3R⁶, wherein R⁶=2 branched C₄alkyl in meta and        OH in para)(as disclosed in example 6 of WO96/12703);    -   The compound is not        5-[2-(Biphenyl-4-yloxy)-ethyl]-5H-imidazo[4,5-c]pyridine        (X═CH₂CH₂, Y=bond, R¹=hydrogen, R²═H, R³=phenoxy substituted        with 1 R¹⁷ in para, wherein R¹⁷=benzyl; R4=H) (as disclosed in        WO96/11192);    -   The compound is not        5-[2-(4-Phenoxy-phenoxy)-ethyl]-5H-imidazo[4,5-c]pyridine        (X═CH₂CH₂, Y=bond, R¹=hydrogen, R²═H, R³=phenoxy substituted        with 1 R¹⁷ in para, wherein R¹⁷=phenoxy; R4=H) (as disclosed in        WO96/11192);    -   the compound is not not        5-(5-benzyl-2,3-dihydro-benzofuran-2-ylmethyl)-5H-imidazo[4,5-c]pyridine        (as disclosed in WO96/11192:    -   the compound is not        5-[2-[4-(phenylmethyl)phenoxy]ethyl]-5H-imidazo[4,5-c]pyridine        hydrate (as disclosed in WO96/11192);    -   the compound is not        5-[2-[(phenylmethoxy)phenoxy]ethyl]-5H-imidazo[4,5-c]pyridine        (as disclosed in WO96/11192);    -   the compound is not        5-[2-[4-phenoxyphenoxy)ethyl]-5H-imidazo4,5-c]pyridine (as        disclosed in WO96/11192);    -   the compound is not        5-[3-[4-(phenoxyphenoxy)propyl]-5H-imidazo[4,5-c]pyridine (as        disclosed in WO96/21192):    -   the compound is not        5-[2-[4-(4-fluorophenoxy)phenoxy)ethyl]-5H-imidazo[4,5-c]-pyridine        (as disclosed in WO96/11192);    -   the compound is not        5-[3-[4(phenylmethyl)phenoxy)propyl]-5H-imidazo[4,5-c]pyridine        (as disclosed in WO96/11192).    -   The compound is not        [5-(4-Fluorobenzyl)-5H-imidazo[4,5c]pyridin-2-yl]-methylamine        (X═CH₂, Y═NR11, wherein R11=methyl, R1=R²═H, R³-phenyl        substituted with 1 R¹⁷ in para, wherein R⁶ is F, R4=H, R5=H) (as        disclosed in EP76530);    -   The compound is not        2,6-bis(1,1,-dimethylethyl)-4-[[3-(5H-imidazo-[4,5-c]pyridin-5-yl)propyl]thio]-phenol        hydrate (X═CH₂—CH₂—CH₂, Y=bond; R1=hydrogen, R²═H, R³-thiophenyl        substituted with 3 R⁶, wherein R⁶=2 branched C4 yl in meta and        OH in para) (as disclosed in WO96/12703);    -   The compound is not        2,6-bis(1,1,-dimethylethyl)-4-[[2-(5H-imidazo-[4,5-c]pyridin-5-yl)ethyl]thio]-phenol        hydrate (X═S—CH₂—CH₂, Y=bond; R1=hydrogen, R²═H, R³-thiophenyl        substituted with 3 R⁶, wherein R⁶=2 branched C4 alkyl in meta        and OH in para) (as disclosed in WO96/12703):    -   The compound is not        2,6-bis(1,1,-dimethylethyl)-4-[[4-(5H-imidazo-[4,5-c]pyridin-5-yl)butyl]thio]-phenol        hydrate X═S—CH₂—CH₂—CH₂, Y=bond; R1=hydrogen, R²═H,        R³=thiophenyl substituted with 3 R⁶, wherein R⁶=2 branched C4        alkyl in meta and OH in para) (as disclosed in WO96/12703);    -   The compound is not (±)        2,6-bis(1,1,-dimethylethyl)-4-[[2-hydroxy-3-(5H-imidazo-[4,5-c]pyridin-5-yl)butyl]thio]-phenol        hydrate (X═S—CH₂—CHOH—CH₂, Y=bonded; RI132 hydrogen, R²═H,        R³-thiophenyl substituted with 3 R⁶, wherein R⁶=2 branched C4        alkyl in meta and OH in para) (as disclosed in WO96/12703);    -   The compound is not        5-[2-(4-Phenylmethyloxy-phenoxy)-ethyl]-5H-imidazo[4,5-c]pyridine        (X═CH₂CH₂, Y=bond, R1=hydrogen, R²═H, R³=phenoxy substituted        with 1 R¹⁷ in para, wherein R¹⁷=benzyl oxy) (as disclosed in        WO96/11192);    -   The compound is not        5-[3-(4-Phenoxy-phenoxy)-propyl]-5H-imidazo[4,5c]pyridine        (X═CH₂CH₂CH₂, Y=bond, R1=hydrogen, R²═H, R³=phenoxy substituted        with 1 R⁶ in para, wherein R⁶=phenoxy substituted in para with        F; R4═H) (as disclosed in WO96/11192);    -   The compound is not        5-{2-[4-(4-Fluorophenoxy)-phenoxy]-ethyl}-5H-imidazo[4,5-c]pyridine        (X═CH₂CH₂, Y=bond, R1=hydrogen, R²═H, R³=phenoxy substituted        with 1 R⁶ in para, wherein R⁶=phenoxy, substituted in para with        F; R4=H) (as disclosed in WO96/11192);    -   The compound is not        5-[3-(4-Phenylmethyl-phenoxy)-propyl]-5H-imidazo[4,5-c]pyridine        (X═CH₂CH₂CH₂, Y=bond, R1=hydrogen, R²═H, R³=phenoxy substituted        with 1 R⁶ in para, wherein R⁶=benzyl; R4=H) (as disclosed in        WO96/11192);    -   The compound is not        (1H-Indol-3-yl)-[3-(2-methyl-5H-imidazo[4,5-c]pyridine-5-carbonyl)-phenyl]-methanone        (X═—(C═O)— or SO₂, Y═CH₂, R1=H, R²═H, R³=phenyl substituted with        1 R⁶, wherein R⁶ is C(═O)R¹⁸, wherein R¹⁸ is indole) (as        disclosed in U.S. Pat. No. 5,486,525);    -   the compound is not 4 or        3-[(2-methyl-5H-imidazo[4,5c]pyridine-5-yl)methyl]-benzoic acid        alkylester or 5-[4 or        3-(alkoxycarbonyl-phenyl)-methyl]-2-methyl-5H-imidazo[4,5-c]pyridine,        in particular 4 or        3-[(2-methyl-5H-imidazo[4,5-c]pyridin-5-yl)methyl]-methyl ester        (X═CH₂, Y═CH₂, R1=H, R²═H, R³=phenyl substituted at the para or        meta position with 1R¹⁷, wherein R¹⁷ is (C═O)R¹⁸, wherein        R¹⁸=alkoxy) (as disclosed in U.S. Pat. No. 5,486,525)    -   the compound is not        5-[(fluorophenyl)methyl]-2-amino-5-H-imidazo[4,5-c]-pyridine        (XR³=fluorobenzyl, Y═NR¹¹ with R¹¹=methyl, R¹═H, R², R³, R⁴═H)        (as disclosed in U.S. Pat. No. 5,137,896);    -   the compound is not        ((5-[4-(Fluorophenyl)methyl]-5-H-imidazo[4,5-c]-pyridine-2-yl)        methyl)-carbamaat, methyl ester (XR³=fluorobenzyl, Y═C(═O)R12        with R12=methyl, R¹═H, R², R³, R⁴=H) (as disclosed in U.S. Pat.        No. 5,137,896);    -   the compound is not        5-(4-Chlorophenylmethyl)-2-(piperidin-1-ylmethyl)-5H-imidazo(4,5-c]pyridine        and its dihydrochloride salt (XR³=chlorobenzyl, Y═—CH₂—,        R¹=piperidinyl) (as disclosed in Justus Liebis Annalen der        Chemie (1971), 747, 158-171);    -   the compound is not        5-(4-Chlorophenylmethyl)-2-(4-methyl-piperazin-1-ylmethyl)-5H-imidazo[4,5-c]pyridine        (XR³=chlorobenzyl, Y═—CH₂—, R¹=piperazinyl, R⁶=methyl) (as        disclosed in Journal of the Chemical Society [section B]:        Physical Organic (1966), 4, 285-291);    -   the compound is not        5-[5-(5-azabenzimidazolyl)methyl)-1-(4-cyanobenzyl)imidazole (as        disclosed in WO99/27929)

Particularly, the invention relates to a compound according to thegeneral formula (Z) and/or A as described above wherein,

-   -   if Y is a bond and R¹ is an aryl, this aryl is not phenyl para        substituted with OH and optionally further substituted with        methyl, methoxy, nitro, diethylamino, Cl, Br, or F; or, if Y is        a bond and R1 is a aryl para substituted with OH and optionally        further substituted with methyl, methoxy, nitro, diethylamino,        Cl, Br, or F, and X is an alkylene, R³ is not a heterocyclic        ring containing N;        -   and/or    -   if Y is a bond or (CH₂)₁₋₆, R¹ is H, X is CH₂ and R³ is phenyl        with 1R¹⁷, wherein R¹⁷ is C(═O)R¹⁸, then R¹⁸ is selected from H;        OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl an        amino acid residue linked through an amino group thereof; i.e.        R18 is not a C₃₋₁₀ cycloalkyl or C₄₋₁₀ cycloalkenyl;        -   and/or    -   if Y is a bond or (CH2)₁₋₆, then R¹ is an aryl unsubstituted or        substituted with one or more R⁶, heterocyclic ring unsubstituted        or substituted with one or more R⁶, C₃₋₁₀ cycloalkyl        unsubstituted or substituted with one or more R⁶ and C₄₋₁₀        cycloalkenyl unsubstituted or substituted with one or more R⁶;        i.e. YR1 is not H or C₁₋₆ alkyl;        -   and/or    -   if Y is a bond or (CH2)₁₋₆, R¹ is H, and R³ is a 5 membered        heterocyclic ring with one R¹⁷, wherein R17 is C(═O)R18 and R18        is NR¹⁵R¹⁶, then R¹⁵ and R¹⁶ are not a C₁₋₁₈ alkyl or a        cycloalkyl; or    -   if Y is a bond or (CH2)₁₋₆, and R¹ is H, and R³ is a 5 membered        heterocyclic ring with one R¹⁷, wherein R17 is C(═O)R18 then R18        is selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; aryl an amino acid        residue linked through an amino group thereof; i.e. R¹⁸ is not        NR¹⁵R¹⁶; or        -   if Y is a bond or (CH2)₁₋₆, R¹ is H, X is —CH2- and R³ is            phenyl, substituted with one R¹⁷, then R¹⁷ is independently            selected from the group hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈            alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀            cycloalkyl, C₃₋₁₀ cycloalkenyl or C₃₋₁₀ cycloalkynyl;            halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═S)R¹⁸; SH;            aryl; aryloxy; arylthio; arylalkyl; arylalkyloxy (optionally            a oxybenzyl); arylalkylthio (optionally a benzylthio); 5 or            6 membered heterocyclic, oxyheterocyclic or thioheterocyclic            ring; C₁₋₁₈ hydroxyalkyl; and each of said aryl, aryloxy,            arylthio, arylalkyl, arylalkyloxy (optionally a oxybenzyl),            arylalkylthio (optionally a benzylthio), 5 or 6 membered            heterocyclic, oxyheterocyclic or thioheterocyclic ring,            C₁₋₁₈ hydroxyalkyl is optionally substituted with 1 or more            R¹⁹; i.e., then R¹⁷ is not (C═O)R¹⁸;        -   and/or    -   if Y is a bond or (CH2)₁₋₆, and R¹ is H, and R³ is a 5 membered        heterocyclic ring with one R¹⁷ , wherein R17 is C(═O)R18 then        R18 is selected from H; OH; C₁₋₁₈ alkyl; aryl, NR¹⁵R¹⁶; i.e.        wherein R¹⁸ is not C₁₋₁₈ alkoxy;        -   and/or    -   if Y is a bond or (CH2)₁₋₆, and R¹ is H, and R³ is a 5 membered        heterocyclic ring with one R¹⁷, wherein R¹⁷ is C(═O)R¹⁸ then R¹⁸        is selected from OH; C₁₋₁₈ alkyl; C₁₋₁₈ alkoxy; aryl, NR¹⁵R¹⁶;        i.e. wherein R¹⁸ is not H;        -   and/or    -   if Y is a bond, R¹ is hydrogen, X is an alkyl and R³ is an aryl        thio substituted with 3 R¹⁷, and 1 R¹⁷ is OH in para, the        remaining R¹⁷ are independently selected from the group        consisting of hydrogen; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈        alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀ cycloalkenyl or        C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; arylalkyloxy (optionally a oxybenzyl); arylalkylthio        (optionally a benzylthio); 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈ hydroxyalkyl;        and each of said aryl, aryloxy, arylthio, arylalkyl,        arylalkyloxy (optionally a oxybenzyl), arylalkylthio (optionally        a benzylthio), 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl is optionally        substituted with 1 or more R¹⁹; i.e. the remaining R¹⁷ are not a        C₁₋₈ alkyl;        -   and/or    -   if Y is a bond, R¹ is a hydrogen, X is —(CH2-CH2)-, then R³ is        selected from aryl; aryloxy; aryl-NR¹⁰—; 5 or 6 membered        heterocyclic, oxyheterocyclic or thioheterocyclic ring; and each        of said aryl, aryloxy, aryl-NR¹⁰—, 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring is optionally        substituted with one or more R¹⁷; C₃₋₁₀ cycloalkyl,        oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenyl with the        proviso that the double bond cannot be adjacent to a nitrogen; H        with the proviso that if X is an alkylene, an alkenylene or an        alkynylene, then X comprises at least 5 carbon atoms; i.e. then        R³ is not an arylthio or if X is —(CH2CH2)-S, R³ is not an aryl;        -   and/or    -   if Y is a bond, R¹ is H, X is an alkylene and R³ is phenoxy, R¹⁷        is independently selected from the group hydrogen; C₁₋₁₈, alkyl;        C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio;        C₃₋₁₀ cycloalkyl, C₃₋₁₀ cycloalkenyl or C₃₋₁₀ cycloalkynyl;        halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹;        SH; aryl; arylthio; arylalkyl (except benzyl); arylalkyloxy        (except oxybenzyl); arylalkylthio (optionally a benzylthio); 5        or 6 membered heterocyclic, oxyheterocyclic or thioheterocyclic        ring; C₁₋₁₈ hydroxyalkyl; and each of said aryl, aryloxy,        arylthio, arylalkyl, arylalkyloxy (optionally a oxybenzyl),        arylalkylthio (optionally a benzylthio), 5 or 6 membered        heterocyclic, oxyheterocyclic or thioheterocyclic ring, C₁₋₁₈        hydroxyalkyl is optionally substituted with 1 or more R¹⁹; i.e.        if R³ is phenoxy, R¹⁷ is not benzyl or phenoxy or oxybenzyl;        -   and/or    -   if XR³ is fluorobenzyl, R², R³, R⁴ are R¹═H and Y is NR¹¹, R¹¹        is selected from H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl; 5-6 membered heterocyclin        ring; an amino acid residue linked through a carboxyl group        thereof, i.e. R¹¹ is not methyl or C(═O)R¹²;    -   If X is CH₂ and R³ is a phenyl substituted in para with Cl, and        Y is CH₂, then R¹ is not piperazinyl, or        -   If X is CH₂ and R³ is a phenyl substituted in para with Cl,            and Y is CH₂, then R¹ heterocyclic ring is aromatic;        -   and/or    -   If R⁵ is an aryl, aryloxy or benzyl group, R¹ is not H or C₃₋₁₀        alkyl, or        -   If R¹ is H or C₃₋₁₀alkyl, then R⁵ is selected from hydrogen;            C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy;            C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;            haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; arylthio; arylalkyl (except            benzyl); C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀            cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀ cycloalkenyl;            C₃₋₁₀ cycloalkynyl; 5 or 6 membered heterocyclic,            oxyheterocyclic or thioheterocyclic ring, i.e., R⁵ is not an            aryl, aryloxy or benzyl;

The compounds of the invention optionally exclude those compoundsaccording to the general formula (Z) and/or (A) as described above,wherein YR¹ is not hydrogen, an unsubstituted C₃₋₁₀ cycloalkyl, or aC₁₋₆ alkyl.

The compounds of the invention optionally exclude those compoundsaccording to the general formula (Z) and/or (A) as described above,wherein Y R¹ is not phenyl para substituted with OH.

The compounds of the invention optionally exclude those compoundsaccording to the general formula (Z) and/or (A) as described above,wherein R¹ is not H, Y is not NR¹¹ with R11 C₁₋₆ alkyl or methyl, and/orYR¹ is not monomethylamino.

The compounds of the invention optionally exclude those compoundsaccording to the general formula (Z) and/or (A) as described above,wherein R¹ is a phenyl substituted with 1R6, R6 is C(═O)R¹⁸ and R¹⁸ ist-butoxy.

The compounds of the invention optionally exclude those compoundsaccording to the general formula (Z) and/or (A) as described above,wherein R¹ is not piperidinyl and is not piperazinyl substituted withmethyl.

The compounds of this invention optionally exclude those in which XR³ isequivalent to the substructure —(CH₂)n-Y′—C(O)N(R₁′)(R₂′) set forth oncolumn 1, line 49 to column 2 line 38 of U.S. Pat. No. 5,302,601 whereinR₁′ and R₂′ are each independently selected from hydrogen; straight orbranched chain alkyl of 1 to 15 carbon atoms: cycloalkyl having 3 to 8carbon atoms; substituted cycloalkyl which can be substituted one ormore by alkyl of 1 to 6 carbon atoms; bicycloalkyl having 3 to 8 carbonatoms in each ring; heterocyclicalkyl having 4 to 8 carbon atoms whichcan be optionally substituted by alkyl of 1 to 6 carbon atoms;heteroaromatic having 5 or 6 carbon atoms which can be optionallysubstituted by alkyl having 1 to 6 carbon atoms; phenyl; substitutedphenyl which can be substituted one or more by a group independentlyselected from alkyl having 1 to 6 carbon atoms or halogen; straight orbranched alkenyl having 3 to 15 carbon atoms with the proviso that thedouble bond of the alkenyl group cannot be adjacent to the nitrogen;cycloalkenyl having 5 to 8 carbon atoms with the proviso that the doublebond cannot be adjacent to the nitrogen; and R₁′ and R₂′ cannot both behydrogen; Y′ is phenyl or phenyl substituted once or more than at one ormore of the 2, 3, 5 or 6 positions of the phenyl ring by substituentsindependently selected from the group consisting of alkoxy having 1 to 6carbon atoms; halogen wherein the halogen is selected from bromo,fluoro, or chloro; straight or branched chain alkyl having 1 to 6 carbonatoms: substituted straight or branched chain alkyl which can besubstituted one or more by halogen; thioalkyl wherein the alkyl has 1 to6 carbon atoms; alkoxyalkyl wherein the alkyl groups are each 1 to 6carbon atoms; hydroxyalkyl wherein the alkyl has 1 to 6 carbon atoms;alkylthioalkyl wherein the alkyl groups are each 1 to 6 carbon atoms;cyano; mercaptoalkyl wherein the alkyl has 1 to 6 carbon atoms; hydroxy;amino; alkylamino wherein the alkyl group has 1 to 6 carbon atoms; anddialkylamino wherein the alkyl groups are each 1 to 6 carbon atoms; n isan unit integer 1 to 5 and the comparable disclosure in any member ofthe patent family of U.S. Pat. No. 5,302,601, which disclosure isherewith expressly incorporated by reference.

The compounds of this invention optionally exclude those in which R⁵contains any of the substituents designated as <<Ar>> in WO 00/39127(incorporated expressly herein by reference), in particular aryl,arylphenoxy, or benzyl.

Typically, the compounds of this invention do not include the compoundsof example 35 of U.S. Pat. No. 5,302,601, example 6 of U.S. Pat. No.4,990,518, examples 1 to 5 of U.S. Pat. No. 4,988,707, examples 3 and/or11 of WO 96/12703 and/or compounds 340A, 347C, 349C, 351 C, 355C and/or356 C of WO 96/11192 and/or their methylene homologues, the disclosureof which are herewith expressly incorporated by reference

Optionally, the compounds of this invention also exclude all methylenehomologues of known compounds which are excluded from the scope of thisinvention.

The compounds of this invention optionally exclude those in which XR3 isequivalent to the substructure —(CH2)n-Het-C(O)—N(R1)(R2) set forth oncolumn 1, line 41 to column 2 line 24 of U.S. Pat. No. 4,990,518 and thecomparable disclosure in any member of the patent family of U.S. Pat.No. 4,990,518, which disclosure is herewith expressly incorporated byreference.

Typically the compounds of this invention do not include the compoundexpressly disclosed in EP 76530, EP 1 162 196, EP 1132 381, U.S. Pat.No. 5,486,525, U.S. Pat. No. 5,137,896, U.S. Pat. No. 5,227,384, U.S.Pat. No. 4,914,108, U.S. Pat. No. 5,302,601, U.S. Pat. No. 5,208,242,U.S. Pat. No. 4,990,518, U.S. Pat. No. 4,988,707, DE 4,211,474, DE4,230,464, WO 00/39127, WO 00/40586, WO 00/40583, WO 00/39127, WO00/20416, WO99/27929, GB2158440, WO6111192. EP3444414, WO9516687,Chemical Abstracts acc no.110:165603, Chemical Abstracts accno.132:22537 and any family member thereof in Chemical Abstracts acc no1987:18435 and Chemical Abstracts acc no. 1983:594812 and overlap withthe compounds described in the preset description, the disclosure ofwhich is herewith expressly incorporated by reference.

Typically the compounds of this invention do not include the compoundsexpressly disclosed in EP 76530, EP 1 162 196, EP 1132 381, U.S. Pat.No. 5,486,525, U.S. Pat. No. 5,137,896, U.S. Pat. No. 5,227,384, U.S.Pat. No. 4,914,108, WO 00/39127, WO 00/40586, WO99/27929, GB2158440,WO6111192, EP3444414, WO9516687, Chemical Abstracts ace no. 1987:18435,Chemical Abstracts acc no.110:165603, Chemical Abstracts accno.132:222537 and Chemical Abstracts acc no. 1983:594812 and over whichthe claims of this application are not novel or do not posses aninventive step; the disclosure of these compounds is herewith expresslyincorporated by reference.

Typically the compounds of this invention do not include the compoundsexpressly disclosed in Justus Liebigs Annalen der Chemie (1971), 747,158-171 or in the Journal of the Chemical Society [section B]: PhysicalOrganic (1966), 4, 285-291 and over which the claims of this applicationare not novel or do not posses an inventive step; the disclosure ofthese compounds is herewith expressly incorporated by reference.

Optionally, the compounds of this invention include only those compoundswherein YR1 is none of the substituents designated R13 in column 5,lines 22-38 of U.S. Pat. No. 5,486,525 and/or R2 and/or R5 are none ofthe substituents collectively designated R14 and R15 in column 5, lines38-53 of U.S. Pat. No. 5,486,525, which is herewith incorporatedexpressly by reference to the extent that such substituents overlap withthose set forth herein.

According to a particular aspect the present invention relates tocompounds of the formula (Z) and/or (A), described above wherein R¹ is aphenyl optionally substituted with a benzyloxy, and wherein R¹⁹ at metais phenyl optionally substituted with a halogen, (particularly chloro)in para, and R¹⁹ at ortho is H, nitro, amino, mono- or di(C₁₋₆alkyl)-substituted amino, NHC(O)(C₁₋₆ alkyl); methoxysulfonamide orC(O)R²², wherein R²² is NR²³R²⁴ as defined above. Optionally R²³ and R²⁴are C₁₋₆ alkyl taken together with to form a hydroxy-substituted6-membered saturated N-heterocyclic ring.

One embodiment of this second aspect of the present invention relates tocompounds according to the general formula (I), pharmaceuticallyacceptable salts, tautomers, and isomers thereof, wherein:

wherein:

-   -   R¹ is selected from hydrogen; aryl unsubstituted or substituted        with one or more R⁶, heterocyclic ring unsubstituted or        substituted with one or more R⁶, C₃₋₁₀ cycloalkyl unsubstituted        or substituted with one or more R⁶ and C₄₋₁₀ cycloalkenyl        unsubstituted or substituted with one or more R⁶;    -   Y is selected from the group consisting of a single bond, O;        S(O)_(m); NR¹¹; and a divalent, saturated or unsaturated,        substituted or unsubstituted C₁-C₁₀ hydrocarbon group optionally        including one or more heteroatoms in the main chain, said        heteroatoms being selected from the groups consisting of O, S,        and N; such as C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene,        —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—, —S—(CH₂)₁₋₅—,        —(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—, —(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄—        and C₃₋₁₀ cycloalkylidene;    -   Each R² and R⁴ is independently selected from the group        consisting of hydrogen C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂;        NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy;        arylthio; arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio; C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   X is selected from the group consisting of a divalent, saturated        or unsaturated, substituted or unsubstituted C₁-C₁₀ hydrocarbon        group optionally including one or more heteroatoms in the main        chain (provided that the heteroatom is not linked to N of the        nucleus), said heteroatoms being selected from the group        consisting of O, S, and N; such as C₁₋₆ alkylene, (for example        —CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂),        —(CH₂)₂₋₄—O—(CH₂)₂₋₄—, —(CH₂)₂₋₄—S—(CH₂)₂₋₄—,        —(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene        (such as —CH═CH—CH₂—), C₂₋₆ alkynylene;    -   m is any integer from 0 to 2;    -   R³ is selected from the group consisting of aryl; aryloxy;        arylthio; aryl-NR¹⁰—; 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; and each of said aryl,        aryloxy, arylthio, aryl-NR¹⁰—, 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring is optionally        substituted with one or more R¹⁷; C₃₋₁₀ cycloalkyl,        oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenyl with the        proviso that the double bond cannot be adjacent to a nitrogen; H        with the proviso that if X is an alkylene, an alkenylene or an        alkynylene, then X comprises at least 5 carbon atoms;    -   R⁵ is independently selected from the group consisting of        hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈        alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   Each R⁶ and R¹⁷ is independently selected from the group        consisting of hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸;        OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; arylalkyloxy (optionally a oxybenzyl); arylalkylthio        (optionally a benzylthio); 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈ hydroxyalkyl;        and each of said aryl, aryloxy, arylthio, arylalkyl,        arylalkyloxy (optionally a oxybenzyl), arylalkylthio (optionally        a benzylthio), 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl is optionally        substituted with 1 or more R¹⁹.    -   Each R⁷ and R⁸ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6 membered heterocyclic ring;        C(═O)R¹²; C(═S)R¹²; an amino acid residue linked through a        carboxyl group thereof; alternatively, R⁷ and R⁸, together with        the nitrogen to which they are attached, combine to form a 5-6        membered heterocyclic ring;    -   Each R⁹ and R¹⁸ is independently selected from the group        consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl an        amino acid residue linked through an amino group thereof;    -   Each R¹⁰ and R¹¹ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl; C(═O)R¹²; 5-6 membered        heterocyclin ring; an amino acid residue linked through a        carboxyl group thereof;    -   R¹² is independently selected from the group consisting of H;        C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; an amino acid residue linked through an amino        group thereof;    -   Each R¹³ and R¹⁴ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═S)R¹²; an amino        acid residue linked through a carboxyl group thereof;    -   Each R¹⁵ and R¹⁶ is independently selected from the group        consisting of H; C-₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl;        aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid        residue linked through a carboxyl group thereof;    -   R¹⁹ is independently selected from the group consisting of H;        C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy, preferably C₁₋₆ alkoxy; C₁₋₁₈ alkylthio;        C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C₄₋₁₀ cycloalkynyl;        halogen; OH; CN; NO₂; NR²⁰R²¹; OCF₃; haloalkyl; C(═O)R²²;        C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆ alkyl); aryl;        aryloxy; arylthio; arylalkyl; and each of said aryl, aryloxy,        arylthio, arylalkyl substituted with 1 or more halogens,        particularly a phenyl substituted with 1-2 halogens;        hydroxyalkyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring each unsubstituted or substituted with 1        or more halogens;    -   Each R²⁰ and R²¹ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈        alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; C(═O)R¹², C(═S)R¹²;    -   R²² is independently selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈        alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴; aryl; C₃₋₁₀ cycloalkyl,; C₁₋₁₀        cycloalkenyl;    -   Each R²³ and R²⁴ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl, preferably C₂₋₃ alkyl,        wherein C₂₋₃ alkyl taken together with N of R²² can form a        saturated heterocycle, which heterocycle is optionally        substituted with OH or aryl or an amino acid residue.

According to another particular embodiment, the present inventionrelates to compounds according to the general formula (I),pharmaceutically acceptable salts, tautomers, and isomers thereof,wherein:

-   -   R¹ is selected from hydrogen; phenyl unsubstituted or        substituted with 1-3 R⁶; 5 or 6 membered heterocyclic ring,        optionally benzo-added, containing 1-3 heteroatoms selected from        the group O, N, and S, unsubstituted or substituted with 1-2 R⁶;        1-naphthyl unsubstituted or substituted with 1-3 R⁶; 2-naphthyl        unsubstituted or substituted with 1-3 R⁶; C₃₋₁₀ cycloalkyl,        particularly C₃₋₇ cycloalkyl; C₅₋₇ cycloalkenyl with the proviso        that the double bond cannot be adjacent to a nitrogen;    -   Y is selected from the group —(CH₂)₀₋₆—; O; S; NR¹¹; —CH(CH₃)—;        —OCH₂—; —CH₂O—; —OCH₂—CH₂—; —CH₂—CH₂O—; —CH₂—O—CH₂—;        —(CH₂)₀₋₅—S—; —S—(CH₂)₀₋₅—; —(CH₂)₀₋₂—S—(CH₂)₀₋₂—;        —NR¹¹—(CH₂)₀₋₅—; —(CH₂)₀₋₅—NR¹¹—; —CH₂—NR¹¹—CH₂—; —C(CH₃)₂—;        (cis or trans) —CH₂—CH═CH—; (cis or trans) —CH═CH—CH₂—;    -   Each R², R⁴ and R⁵ is independently selected from hydrogen;        straight or branched C₁₋₁₈ alkoxy, particularly C₁₋₆ alkoxy;        straight or branched C₁₋₁₈ alkyl particularly C₁₋₆ alkyl; F; Cl;        Br; I; OH; CN; NO₂; NR⁷R⁸; OCF₃; CF₃; C(═O)R⁹; phenyl; phenoxy;        benzyl; hydroxymethyl;    -   X is selected from the group —CH₂—; —CH(CH₃)—; —CH₂—CH₂—;        —CH₂—CH₂—CH₂—; —CH₂—CH₂—CH₂—CH₂; —OCH₂—CH₂—; —SCH₂—CH₂—;        —NR¹⁰—CH₂—CH₂—; C₃₋₇ cycloalkylidene; —C(CH₃)₂—;        —CH₂—CH(CH₃)—CH₂—; —CH(CH₃)—CH₂—CH₂—; —CH₂—CH₂—CH(CH₃)—;        —CH═CH—CH₂—;    -   R³ is selected from unsubstituted or phenyl substituted with 1-3        R¹⁷; 5 or 6 membered heterocyclic ring, containing 1-3        heteroatoms selected from the group O, N, and S, unsubstituted        or substituted with 1-2 R¹⁷; 1-naphthyl unsubstituted or        substituted with 1-3 R¹⁷; 2-naphthyl unsubstituted or        substituted with 1-3 R¹⁷; C₃₋₁₀ cycloalkyl, particularly C₃₋₇        cycloalkyl; C₅₋₇ cycloalkenyl with the proviso that the double        bond cannot be adjacent to a nitrogen;    -   Each R⁶ and R¹⁷ is independently selected from the group H;        straight or branched C₁₋₆ alkoxy; straight or branched C₁₋₆        alkyl; F; Cl; Br; I; OH; CN; NO₂; NR¹³R¹⁴; OCF₃; CF₃; C(═O)R¹⁸;        unsubstituted phenyl or phenyl substituted with 1-3 R¹⁹; 5 or 6        membered heterocycles, optionally benzo-added, containing 1-3        heteroatoms selected from O, N and S, unsubstituted or        substituted with 1 or 2 R¹⁹; 2-naphthyl unsubstituted or        substituted with 1-3 R¹⁹; C₃₋₇ cycloalkyl; C₅₋₇ cycloalkenyl,        phenoxy; benzyl; hydroxymethyl;    -   Each R⁷ and R⁸ is independently selected from H; straight or        branched C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; phenyl; C(═O)R¹²;        alternatively, R⁷ and R⁸, together with the nitrogen to which        they are attached, combine to form a 5-6 membered ring;    -   Each R⁹ and R¹⁸ is independently selected from H; OH; straight        or branched C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; straight or        branched C₁₋₁₈ alkoxy, preferably C₁₋₆ alkoxy; NR¹⁵R¹⁶; phenyl;    -   Each R¹⁰ and R¹¹ is independently selected from the group H;        C₁₋₁₈ alkyl, preferably C₁₋₆ straight or branched alkyl; phenyl;    -   Each R¹² is selected from the group H; C₁₋₁₈ alkyl, preferably        C₁₋₆ straight or branched alkyl; phenyl;    -   Each R¹³ and R¹⁴ is independently selected from H; straight or        branched C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; phenyl; C(═O)R¹²;    -   Each R¹⁵ and R¹⁶ is independently selected from the group H;        C₁₋₆ straight or branched alkyl; phenyl;    -   R¹⁹ is selected from the group H; straight or branched C₁₋₆        alkoxy; straight or branched C₁₋₆ alkyl; F; Cl, Br; OH; NO2;        NR²⁰R²¹; OCF3, C(═O)R²²; phenyl; phenoxy; benzyl; hydroxymethyl;    -   Each R²⁰ and R²¹ is independently selected from H; straight or        branched C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; phenyl; C(═O)R¹²;    -   R²² is selected from H; OH; straight or branched C₁₋₆ alkyl;        straight or branched C₁₋₁₈ alkoxy, preferably C₁₋₆ alkoxy;        NR²³R²⁴; phenyl;    -   Each R²³ and R²⁴ is independently selected from the group H;        C₁₋₁₈ alkyl, preferably C₁₋₆ straight or branched alkyl; phenyl.

Another embodiment of present invention relates to compounds of formula(II), which are related to the general Formula (I), but wherein R¹ isdirectly linked to the imidazo[4,5-c]pyridine ring structure,pharmaceutically acceptable salts, tautomers, and isomers thereof andtheir use in a treatment of viral infection or to manufacture amedicament to treat viral infections, wherein:

-   -   R¹ is selected from phenyl substituted with 0-3 R⁶; 5 or 6        membered heterocyclic ring containing 1-3 heteroatoms selected        from the group O, N, and S, substituted with 0-2 R⁶; 1-naphthyl        substituted with 0-3 R⁶; 2-naphthyl substituted with 0-3 R⁶;        C₃₋₇ cycloalkyl; C₄₋₅₋₇₁₀ cycloalkenyl;    -   R², R⁴ and R⁵ are independently selected from hydrogen; straight        or branched C₁₋₆ alkoxy; straight or branched C₁₋₆ alkyl; F; Cl;        Br; I; OH; CN; NO₂; NR⁷R⁸; OCF₃; CF₃; C(═O)R⁹; phenyl; phenoxy;        benzyl; hydroxymethyl;    -   X is selected from the group —CH₂—; —CH(CH₃)—; —CH₂—CH₂—;        —CH₂—CH₂—CH₂—; —CH₂—CH₂—CH₂—CH₂; —OCH₂—CH₂—; —SCH₂—CH₂—;        —NR¹⁰—CH₂—CH₂—; C₃₋₇ cycloalkylidene; —C(CH₃)₂;        —CH₂—CH(CH₃)—CH₂—; —CH(CH₃)—CH₂—CH₂—; —CH₂—CH₂—CH(CH₃)—;        —CH═CH—CH₂—;    -   R³ is selected from phenyl substituted with 0-3 R¹⁷;        (benzoannellated) 5 or 6 membered aromatic heterocyclic ring        containing 1-3 heteroatoms selected from the group O, N, and S,        substituted with 0-2 R¹⁷; 1-naphthyl substituted with 0-3 R¹⁷;        2-naphthyl substituted with 0-3 R¹⁷; C₃₋₇ cycloalkyl; C₄₋₁₀        cycloalkenyl with the proviso that the double bond cannot be        adjacent to a nitrogen;    -   R⁶ and R¹⁷ are independently selected from the group H; straight        or branched C₁₋₆ alkoxy; straight or branched C₁₋₆ alkyl; F; Cl;        Br; I; OH; CN; NO₂; NR¹³R¹⁴; OCF₃; CF₃; C(═O)R¹⁸; phenyl;        phenoxy; benzyl; hydroxymethyl;    -   R⁷ and R⁸ are independently selected from H; straight or        branched C₁₋₆ alkyl; phenyl; C(═O)R¹² or R⁷ and R⁸, together        with the nitrogen to which they are attached, combine to form a        5-6 membered ring;    -   R⁹ and R¹⁸ are independently selected from H; OH; straight or        branched C₁₋₆ alkyl; straight or branched C₁₋₆ alkoxy; NR¹⁵R¹⁶;        phenyl;    -   R¹⁰ is selected from the group H; C₁₋₆ straight or branched        alkyl; phenyl;    -   R¹² is selected from the group H; C₁₋₆ straight or branched        alkyl; phenyl;    -   R¹³ and R¹⁴ are independently selected from H; straight or        branched C₁₋₆ alkyl; phenyl; C(═O)R¹²;    -   R¹⁵ and R¹⁶ are independently selected from the group H; C₁₋₆        straight or branched alkyl; phenyl;

Another embodiment of the present invention relates to compounds offormula (II), pharmaceutically acceptable salts, tautomers, and isomersthereof and their use in a treatment of viral infection or tomanufacture a medicament to treat viral infection, wherein:

-   -   R¹ is selected from phenyl substituted with 0-3 R⁶; 5 or 6        membered heterocyclic ring containing 1-3 heteroatoms selected        from the group O, N, and S, substituted with 0-2 R⁶; 1-naphthyl        substituted with 0-3 R⁶; 2-naphthyl substituted with 0-3 R⁶;        C₃₋₇ cycloalkyl; C₄₅₋₇₋₁₀ cycloalkenyl;    -   R², R⁴ and R⁵ are independently selected from hydrogen; straight        or branched C₁₋₆ alkoxy; straight or branched C₁₋₆ alkyl; F; Cl;        Br; I; OH; CN; NO₂; NR⁷R⁸; OCF₃; CF₃; C(═O)R⁹; phenyl; phenoxy;        benzyl; hydroxymethyl;    -   X is selected from the group —CH₂—; —CH(CH₃)—; —CH₂—CH₂—CH₂—;        —OCH₂—CH₂—; —CH═CH—CH₂—;    -   R³ is selected from phenyl substituted with 0-3 R¹⁷;        (benzoannellated) 5 or 6 membered aromatic heterocyclic ring        containing 1-3 heteroatoms selected from the group O, N, and S,        substituted with 0-2 R¹⁷; 1-naphthyl substituted with 0-3 R¹⁷;        2-naphthyl substituted with 0-3 R¹⁷; C₃₋₇ cycloalkyl; C₄₋₇        cycloalkenyl with the proviso that the double bond cannot be        adjacent to a nitrogen;    -   R⁶ and R¹⁷ are independently selected from the group H; straight        or branched C₁₋₆ alkoxy; straight or branched C₁₋₆ alkyl; F; Cl;        Br; I; OH; CN; NO₂; NR¹³R¹⁴; OCF₃; CF₃; C(═O)R¹⁸; phenyl;        phenoxy; benzyl; hydroxymethyl;    -   R⁷ and R⁸ are independently selected from H; straight or        branched C₁₋₆ alkyl; phenyl; C(═O)R¹²; alternatively, R⁷ and R⁸,        together with the nitrogen to which they are attached, combine        to form a 5-6 membered ring;    -   R⁹ and R¹⁸ are independently selected from H; OH; straight or        branched C₁₋₆ alkyl; straight or branched C₁₋₆ alkoxy; NR¹⁵R¹⁶;        phenyl;    -   R¹² is selected from the group H; C₁₋₆ straight or branched        alkyl; phenyl;    -   R¹³ and R¹⁴ are independently selected from H; straight or        branched C₁₋₆ alkyl; phenyl; C(═O)R¹²;    -   R¹⁵ and R¹⁶ are independently selected from the group H; C₁₋₆        straight or branched alkyl; phenyl;

Another embodiment of present invention relates to compounds of formula(II), pharmaceutically acceptable salts, tautomers, and isomers andtheir use in a treatment of viral infection or to manufacture amedicament to treat viral infection, wherein:

-   -   R¹ is selected from phenyl unsubstituted or substituted with 1-3        R⁶; 5 or 6 membered heterocyclic ring containing 1-3 heteroatoms        selected from the group O, N, and S, unsubstituted or        substituted with 1-2 R⁶; 1-naphthyl unsubstituted or substituted        with 1-3 R⁶; 2-naphthyl unsubstituted or substituted with 1-3        R⁶; C₃₋₇ cycloalkyl; C₅₋₇ cycloalkenyl;    -   R², R⁴ and R⁵ are hydrogen;    -   X is selected from the group —CH₂—; —CH(CH₃)—; —CH₂—CH₂—CH₂—;        —OCH₂—CH₂—; —CH═CH—CH₂—;    -   R³ is selected from phenyl unsubstituted or substituted with 1-3        R¹⁷; (benzoannellated) 5 or 6 membered aromatic heterocyclic        ring containing 1-3 heteroatoms selected from the group O, N,        and S, unsubstituted or substituted with 1-2 R¹⁷; 1-naphthyl        unsubstituted or substituted with 1-3 R¹⁷; 2-naphthyl        substituted with 0-3 R¹⁷; C₃₋₇ cycloalkyl; C₅₋₇ cycloalkenyl        with the proviso that the double bond cannot be adjacent to a        nitrogen;    -   Each R⁶ and R¹⁷ is independently selected from the group H;        straight or branched C₁₋₆ alkoxy; straight or branched C₁₋₆        alkyl; F; Cl; Br; I; OH; CN; NO₂; NR¹³R¹⁴; OCF₃; CF₃; C(═O)R⁹;        phenyl; phenoxy; benzyl; hydroxymethyl;    -   R⁹ is selected from H; OH; straight or branched C₁₋₆ alkyl;        straight or branched C₁₋₆ alkoxy; NR¹⁵R¹⁶; phenyl;    -   Each R¹³ and R¹⁴ is independently selected from H; straight or        branched C₁₋₆ alkyl; phenyl; C(═O)R¹²;    -   Each R¹⁵ and R¹⁶ is independently selected from the group H;        C₁₋₆ straight or branched alkyl; phenyl;

Yet another embodiment of present invention comprises the compounds offormula (II), pharmaceutically acceptable salts, tautomers, and isomersthereof and their use in a treatment of viral infection or tomanufacture a medicament to treat viral infection, wherein:

-   -   R¹ is selected from phenyl unsubstituted or substituted with 1-3        R⁶; 5 or 6 membered heterocyclic ring containing 1-3 heteroatoms        selected from the group O, N, and S, unsubstituted or        substituted with 1-2 R⁶; 1-naphthyl unsubstituted or substituted        with 1-3 R⁶; 2-naphthyl unsubstituted or substituted with 1-3        R⁶;    -   R², R⁴ and R⁵ are hydrogen;    -   X is selected from —CH₂—; —CH(CH₃)—; —CH₂—CH₂—CH₂—; —OCH₂—CH₂—;        —CH═CH—CH₂—;    -   R³ is selected from phenyl unsubstituted or substituted with 1-3        R¹⁷; 5 or 6 membered aromatic heterocyclic ring containing 1-3        heteroatoms selected from the group O, N, and S, unsubstituted        or substituted with 1-3 R¹⁷; 1-naphthyl unsubstituted or        substituted with 1-3 R¹⁷; 2-naphthyl unsubstituted or        substituted with 1-3 R¹⁷;    -   Each R⁶ and R¹⁷ is independently selected from the group H;        straight or branched C₁₋₆ alkoxy; straight or branched C₁₋₆        alkyl; F; Cl; Br; I; OH; CN; NO₂; NR¹³R¹⁴; OCF₃; CF₃; C(═O)R⁹;        phenyl; phenoxy; benzyl; hydroxymethyl;    -   R⁹ is selected from H; OH; straight or branched C₁₋₆ alkyl;        straight or branched C₁₋₆ alkoxy; NR¹⁵R¹⁶; phenyl;    -   Each R¹³ and R¹⁴ is independently selected from H; straight or        branched C₁₋₆ alkyl; phenyl; C(═O)R¹²;    -   Each R¹⁵ and R¹⁶ is independently selected from the group H;        C₁₋₆ straight or branched alkyl; phenyl.

Particularly, the second embodiment of present invention comprisescompounds of formula (II), pharmaceutically acceptable salts, tautomers,and isomers thereof and their use in a treatment of viral infection orto manufacture a medicament to treat viral infection, wherein:

-   -   R¹ is selected from phenyl unsubstituted or substituted with 1-3        R⁶; 5 or 6 membered heterocyclic ring containing 1-3 heteroatoms        selected from the group O, N, and S, unsubstituted or        substituted with 1-2 R⁶; 1-naphthyl unsubstituted or substituted        with 1-3 R⁶; 2-naphthyl unsubstituted or substituted with 1-3        R⁶;    -   R², R⁴ and R⁵ are hydrogen;    -   X is selected from —CH₂—; —CH(CH₃)—; —CH₂—CH₂—CH₂—; —OCH₂—CH₂—;        —CH═CH—CH₂—;    -   R³ is selected from phenyl unsubstituted or substituted with 1-3        R¹⁷; 5 or 6 membered aromatic heterocyclic ring containing 1-3        heteroatoms selected from the group O, N, and S, unsubstituted        or substituted with 1-2 R¹⁷; 1-naphthyl substituted with 0-3        R¹⁷; 2-naphthyl unsubstituted or substituted with 1-3 R¹⁷;    -   Each R⁶ and R¹⁷ is independently selected from hydrogen;        straight or branched C₁₋₆ alkoxy; straight or branched C₁₋₆        alkyl; F; Cl; Br; I; OH; CN; NO₂; NR¹³R¹⁴; OCF₃; CF₃; C(═O)R⁹;        phenyl; phenoxy; benzyl; hydroxymethyl;    -   R⁹ is selected from H; OH; straight or branched C₁₋₆ alkyl;        straight or branched C₁₋₆ alkoxy; NR¹⁵R¹⁶; phenyl;    -   Each R¹³ and R¹⁴ is independently selected from H; straight or        branched C₁₋₆ alkyl; phenyl; C(═O)R¹²;    -   Each R¹⁵ and R¹⁶ is independently selected from the group H;        C₁₋₆ straight or branched alkyl; phenyl;

A further embodiment of the present invention relates to compounds ofthe formula III:

or a pharmaceutically acceptable acid addition salt thereof

-   -   wherein:    -   R¹ is selected from hydrogen; aryl unsubstituted or substituted        with one or more R⁶, heterocyclic ring unsubstituted or        substituted with one or more R⁶, C₃₋₁₀ cycloalkyl unsubstituted        or substituted with one or more R⁶ and C₄₋₁₀ cycloalkenyl        unsubstituted or substituted with one or more R⁶;    -   Y is selected from the group consisting of a single bond, O;        S(O)_(m); NR¹¹; and a divalent, saturated or unsaturated,        substituted or unsubstituted C₁-C₁₀ hydrocarbon group optionally        including one or more heteroatoms in the main chain, said        heteroatoms being selected from the groups consisting of O, S,        and N; such as C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene,        —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—, —S—(CH₂)₁₋₅—,        —(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—, —(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄—        and C₃₋₁₀ cycloalkylidene;    -   X is selected from the group consisting of a divalent, saturated        or unsaturated, substituted or unsubstituted C₁-C₁₀ hydrocarbon        group optionally including one or more heteroatoms in the main        chain (provided that the heteroatom is not linked to N of the        nucleus), said heteroatoms being selected from the group        consisting of O, S, and N; such as C₁₋₆ alkylene, (for example        —CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂),        —(CH₂)₂₋₄—O—(CH₂)₂₋₄—, —(CH₂)₂₋₄—S—(CH₂)₂₋₄—,        —(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene        (such as —CH═CH—CH₂—), C₂₋₆ alkynylene;    -   m is any integer from 0 to 2;    -   R³ is selected from the group consisting of aryl; aryloxy;        arylthio; aryl-NR¹⁰—; 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; and each of said aryl,        aryloxy, arylthio, aryl-NR¹⁰—, 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring is optionally        substituted with one or more R¹⁷; C₃₋₁₀ cycloalkyl,        oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenyl with the        proviso that the double bond cannot be adjacent to a nitrogen; H        with the proviso that if X is an alkylene, an alkenylene or an        alkynylene, then X comprises at least 5 carbon atoms;    -   R⁴ is independently selected from the group consisting of        hydrogen C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkylenyl; C₁₋₈        alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio; C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   R⁵ is independently selected from the group consisting of        hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈        alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   Each R⁶ and R¹⁷ is independently selected from the group        consisting of hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸;        OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; arylalkyloxy (optionally a oxybenzyl); arylalkylthio        (optionally a benzylthio); 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈ hydroxyalkyl;        and each of said aryl, aryloxy, arylthio, arylalkyl,        arylalkyloxy (optionally a oxybenzyl), arylalkylthio (optionally        a benzylthio), 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl is optionally        substituted with 1 or more R¹⁹;    -   Each R⁷ and R⁸ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6 membered heterocyclic ring;        C(═O)R¹²; C(═S) R¹²; an amino acid residue linked through a        carboxyl group thereof; alternatively, R⁷ and R⁸, together with        the nitrogen to which they are attached, combine to form a 5-6        membered heterocyclic ring;    -   Each R⁹ and R¹⁸ is independently selected from the group        consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl        amino acid residue linked through an amino group thereof;    -   Each R¹⁰ and R¹¹ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl; C(═O)R¹²; 5-6 membered        heterocyclin ring; an amino acid residue linked through a        carboxyl group thereof;    -   R¹² is independently selected from the group consisting of H;        C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; an amino acid residue linked through an amino        group thereof;    -   Each R¹³ and R¹⁴ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═S)R¹²; an amino        acid residue linked through a carboxyl group thereof;    -   Each R¹⁵ and R¹⁶ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl;        aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid        residue linked through a carboxyl group thereof;    -   R¹⁹ is independently selected from the group consisting of H;        C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy, preferably C₁₋₆ alkoxy; C₁₋₁₈ alkylthio;        C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C₄₋₁₀ cycloalkynyl;        halogen; OH; CN; NO₂; NR²⁰R²¹; OCF₃; haloalkyl; C(═O)R²²;        C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆ alkyl); aryl;        aryloxy; arylthio; arylalkyl; and each of said aryl, aryloxy,        arylthio, arylalkyl substituted with 1 or more halogens,        particularly a phenyl substituted with 1-2 halogens;        hydroxyalkyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring each unsubstituted or substituted with 1        or more halogens;    -   Each R²⁰ and R²¹ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈        alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; C(═O)R , C(═S)R¹²;    -   R²² is independently selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈        alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴; aryl; C₃₋₁₀ cycloalkyl, ; C₄₋₁₀        cycloalkenyl;    -   Each R²³ and R²⁴ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl, preferably C₂₋₃ alkyl,        wherein C₂₋₃ alkyl taken together with N of R²² can form a        saturated heterocycle, which heterocycle is optionally        substituted with OH or aryl or an amino acid residue;    -   Z is selected from (═O), (═S), and (═NR²⁷);    -   R²⁵ is selected from the group consisting of of H, C₁₋₁₈ alkyl,        preferably C₁₋₄ alkyl; C₃₋₁₀ cycloalkyl, such as C₅₋₁₀        bicycloalkyl; C₃₋₁₀ cycloalkenyl; (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl;        aryl, such as phenyl; 5 or 6 membered heterocyclic ring, such as        pyridyl; alkylaryl, such as benzyl; and each of said C₁₋₁₈        alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl, C₅₋₁₀ bicycloalkyl,        adamantyl, phenyl, pyridyl and benzyl is optionally substituted        with 1-4 of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OH,        oxybenzyl, and OH; and heterocyclic ring having 3 to 7 carbon        atoms, preferably a saturated heterocyclic ring wherein the        heteroatoms are S, S(O), or S(O)₂ separated from the        imidazopyridyl ring nitrogen atom by at least 2 heterocyclic        ring carbon atoms. Typically R²⁵ is cyclopentyl or cyclohexyl;    -   R²⁷ is selected from the group consisting of H, C₁₋₁₈ alkyl,        C₃₋₁₀ cycloalkyl, (C₃₋₁₀ cycloalkyl)-C₁₋₆ alkyl; aryl;        arylalkyl, such as benzyl.

And pharmaceutical compositions thereof as antiviral drugs.

Another particular embodiment of the present invention relates tocompounds of the formula IV:

or a pharmaceutically acceptable acid addition salt thereof: wherein

-   -   R¹ is selected from hydrogen; aryl unsubstituted or substituted        with one or more R⁶, heterocyclic ring unsubstituted or        substituted with one or more R⁶, C₃₋₁₀ cycloalkyl unsubstituted        or substituted with one or more R⁶ and C₄₋₁₀ cycloalkenyl        unsubstituted or substituted with one or more R⁶;    -   Y is selected from the group consisting of a single bond, O;        S(O)_(m); NR¹¹; and a divalent, saturated or unsaturated,        substituted or unsubstituted C₁-C₁₀ hydrocarbon group optionally        including one or more heteroatoms in the main chain, said        heteroatoms being selected from the groups consisting of O, S,        and N; such as C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene,        —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄, —S—(CH₂)₁₋₅—,        —(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—, —(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄—        and C₃₋₁₀ cycloalkylidene;    -   X is selected from the group consisting of a divalent, saturated        or unsaturated, substituted or unsubstituted C₁-C₁₀ hydrocarbon        group optionally including one or more heteroatoms in the main        chain (provided that the heteroatom is not linked to N of the        nucleus), said heteroatoms being selected from the group        consisting of O, S, and N; such as C₁₋₆ alkylene, (for example        —CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂),        —(CH₂)₂₋₄—O—(CH₂)₂₋₄—, —(CH₂)₂₋₄—S—(CH₂)₂₋₄—,        —(CH₂)2-4—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene        (such as —CH═CH—CH₂—), C₂₋₆ alkynylene;    -   m is any integer from 0 to 2;    -   R³ is selected from the group consisting of aryl; aryloxy;        arylthio; aryl-NR¹⁰—; 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; and each of said aryl,        aryloxy, arylthio, aryl-NR¹⁰—, 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring is optionally        substituted with one or more R¹⁷; C₃₋₁₀ cycloalkyl,        oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenyl with the        proviso that the double bond cannot be adjacent to a nitrogen; H        with the proviso that if X is an alkylene, an alkenylene or an        alkynylene, then X comprises at least 5 carbon atoms;    -   R⁴ is independently selected from the group consisting of        hydrogen C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈        alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloaLkyloxy; C₃₋₁₀ cycloalkylthio; C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   R⁵ is independently selected from the group consisting of        hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈        alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   Each R⁶ and R¹⁷ is independently selected from the group        consisting of hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸;        OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; arylalkyloxy (optionally a oxybenzyl); arylalkylthio        (optionally a benzylthio); 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈ is hydroxyalkyl;        and each of said aryl, aryloxy, arylthio, arylalkyl,        arylalkyloxy (optionally a oxybenzyl), arylalkylthio (optionally        a benzylthio), 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl is optionally        substituted with 1 or more R¹⁹;    -   Each R⁷ and R⁸ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6 membered heterocyclic ring;        C(═O)R¹²; C(═S) R¹²; an amino acid residue linked through a        carboxyl group thereof; alternatively, R⁷ and R⁸, together with        the nitrogen to which they are attached, combine to form a 5-6        membered heterocyclic ring;    -   Each R⁹ and R¹⁸ is independently selected from the group        consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl an        amino acid residue linked through an amino group thereof;    -   Each R¹⁰ and R¹¹ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl; C(═O)R¹²; 5-6 membered        heterocyclin ring; an amino acid residue linked through a        carboxyl group thereof;    -   R¹² is independently selected from the group consisting of H;        C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; an amino acid residue linked through an amino        group thereof;    -   Each R¹³ and R¹⁴ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═S)R¹²; an amino        acid residue linked through a carboxyl group thereof;    -   Each R¹⁵ and R¹⁶ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl;        aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid        residue linked through a carboxyl group thereof;    -   R¹⁹ is independently selected from the group consisting of H;        C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ is alkoxy, preferably C₁₋₆ alkoxy; C₁₋₁₈        alkylthio; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C₄₋₁₀        cycloalkynyl; halogen; OH; CN; NO₂; NR²⁰R²¹; OCF₃; haloalkyl;        C(═O)R²²; C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆        alkyl); aryl; aryloxy; arylthio; arylalkyl; and each of said        aryl, aryloxy, arylthio, arylalkyl substituted with 1 or more        halogens, particularly a phenyl substituted with 1-2 halogens;        hydroxyalkyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring each unsubstituted or substituted with 1        or more halogens;    -   Each R²⁰ and R²¹ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈        alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; C(═O)R¹², C(═S)R¹²;    -   R²² is independently selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈        alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴; aryl; C₃₋₁₀ cycloalkyl,; C₄₋₁₀        cycloalkenyl;    -   Each R²³ and R²⁴ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl, preferably C₂₋₃ alkyl,        wherein C₂₋₃ alkyl taken together with N of R²² can form a        saturated heterocycle, which heterocycle is optionally        substituted with OH or aryl or an amino acid residue;    -   Z is selected from (═O), (═S), and (═NR²⁷);    -   R²⁶ is selected from the group consisting of of H, C₁₋₁₈ alkyl,        preferably C₁₋₄ alkyl; C₃₋₁₀ cycloalkyl, such as C₅₋₁₀        bicycloalkyl; C₃₋₁₀ cycloalkenyl; (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl;        aryl, such as phenyl; 5 or 6 membered heterocyclic ring, such as        pyridyl; alkylaryl, such as benzyl; and each of said C₁₋₁₈        alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl, C₅₋₁₀ bicycloalkyl,        adamantyl, phenyl, pyridyl and benzyl is optionally substituted        with 1-4 of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OH,        oxybenzyl, and OH; and heterocyclic ring having 3 to 7 carbon        atoms, preferably a saturated heterocyclic ring wherein the        heteroatoms are S, S(O), or S(O)₂ separated from the        imidazopyridyl ring nitrogen atom by at least 2 heterocyclic        ring carbon atoms. Typically R²⁶ is cyclopentyl or cyclohexyl;    -   R²⁷ is selected from the group consisting of H, C₁₋₁₈ alkyl,        C₃₋₁₀ cycloalkyl, (C₃₋₁₀ cycloalkyl)-C₁₋₆ alkyl; aryl;        arylalkyl, such as benzyl;    -   and pharmaceutical compositions thereof as antiviral drugs.

A further optional embodiment of the present invention relates tocompounds of the formula V:

or a pharmaceutically acceptable acid addition salt thereof: wherein

-   -   R¹ is selected from hydrogen; aryl unsubstituted or substituted        with one or more R⁶, heterocyclic ring unsubstituted or        substituted with one or more R⁶, C₃₋₁₀ cycloalkyl unsubstituted        or substituted with one or more R⁶ and C₄₋₁₀ cycloalkenyl        unsubstituted or substituted with one or more R⁶;    -   Y is selected from the group consisting of a single bond, O;        S(O)_(m); NR¹¹; and a divalent, saturated or unsaturated,        substituted or unsubstituted C₁-C₁₀ hydrocarbon group optionally        including one or more heteroatoms in the main chain, said        heteroatoms being selected from the groups consisting of O, S,        and N; such as C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene,        —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—, —S—(CH₂)₁₋₅—,        —(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—, —(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄—        and C₃₋₁₀ cycloalkylidene;    -   X is selected from the group consisting of a divalent, saturated        or unsaturated, substituted or unsubstituted C₁-C₁₀ hydrocarbon        group optionally including one or more heteroatoms in the main        chain (provided that the heteroatom is not linked to N of the        nucleus), said heteroatoms being selected from the group        consisting of O, S, and N; such as C₁₋₆ alkylene, (for example        —CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂),        —(CH₂)₂₋₄—O—(CH₂)₂₋₄—, —(CH₂)₂₋₄—S—(CH₂)₂₋₄—,        —(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene        (such as —CH═CH—CH₂—), C₂₋₆ alkynylene;    -   m is any integer from 0 to 2;    -   R² is selected from the group consisting of hydrogen C₁₋₁₈        alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkyl; C₁₋₁₈ alkoxy; C₁₋₁₈        alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl;        C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio; arylalkyl; C₁₋₁₈        hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀ cycloalkyloxy; C₃₋₁₀        cycloalkylthio; C₃₋₁₀ cycloalkenyl; C₃₋₁₀ cycloalkynyl; 5 or 6        membered heterocyclic, oxyheterocyclic or thioheterocyclic ring;    -   R³ is selected from the group consisting of aryl; aryloxy;        arylthio; aryl-NR¹⁰—; 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; and each of said aryl,        aryloxy, arylthio, aryl-NR¹⁰—, 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring is optionally        substituted with one or more R¹⁷; C₃₋₁₀ cycloalkyl,        oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenyl with the        proviso that the double bond cannot be adjacent to a nitrogen; H        with the proviso that if X is an alkylene, an alkenylene or an        alkynylene, then X comprises at least 5 carbon atoms;    -   R⁵ is selected from the group consisting of hydrogen; C₁₋₁₈        alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈        alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl;        C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio; arylalkyl; C₁₋₁₈        hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀ cycloalkyloxy; C₃₋₁₀        cycloalkylthio C₃₋₁₀ cycloalkenyl; C₃₋₁₀ cycloalkynyl; 5 or 6        membered heterocyclic, oxyheterocyclic or thioheterocyclic ring;    -   Each R⁶ and R¹⁷ is independently selected from the group        consisting of hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸;        OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; arylalkyloxy (optionally a oxybenzyl); arylalkylthio        (optionally a benzylthio); 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈ hydroxyalkyl;        and each of said aryl, aryloxy, arylthio, arylalkyl,        arylalkyloxy (optionally a oxybenzyl), arylalkylthio (optionally        a benzylthio), 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl is optionally        substituted with 1 or more R¹⁹;    -   Each R⁷ and R⁸ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6 membered heterocyclic ring;        C(═O)R¹²; C(═S) R¹²; an amino acid residue linked through a        carboxyl group thereof; alternatively, R⁷ and R⁸, together with        the nitrogen to which they are attached, combine to form a 5-6        membered heterocyclic ring;    -   Each R⁹ and R¹⁸ is independently selected from the group        consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl an        amino acid residue linked through an amino group thereof;    -   Each R¹⁰ and R¹¹ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl; C(═O)R¹²; 5-6 membered        heterocyclin ring; an amino acid residue linked through a        carboxyl group thereof;    -   R¹² is independently selected from the group consisting of H;        C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; an amino acid residue linked through an amino        group thereof;    -   Each R¹³ and R¹⁴ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═S)R¹²; an amino        acid residue linked through a carboxyl group thereof;    -   Each R¹⁵ and R¹⁶ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl;        aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid        residue linked through a carboxyl group thereof;    -   R¹⁹ is independently selected from the group consisting of H;        C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₉        alkynyl; C₁₋₁₈ alkoxy, preferably C₁₋₆ alkoxy; C₁₋₁₈ alkylthio;        C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C₄₋₁₀ cycloalkynyl;        halogen; OH; CN; NO₂; NR²⁰R²¹; OCF₃; haloalkyl; C(═O)R²²;        C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆ alkyl); aryl;        aryloxy; arylthio; arylalkyl; and each of said aryl, aryloxy,        arylthio, arylalkyl substituted with 1 or more halogens,        particularly a phenyl substituted with 1-2 halogens;        hydroxyalkyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring each unsubstituted or substituted with 1        or more halogens;    -   Each R²⁰ and R²¹ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈        alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; C(═O)R¹², C(═S)R¹²;    -   R²² is independently selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈        alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴; aryl; C₃₋₁₀ cycloalkyl, ; C₄₋₁₀        cycloalkenyl;    -   Each R²³ and R²⁴ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl, preferably C₂₋₃ alkyl,        wherein C₂₋₃ alkyl taken together with N of R²² can form a        saturated heterocycle, which heterocycle is optionally        substituted with OH or aryl or an amino acid residue;    -   Z is selected from (═O), (═S), and (═NR²⁷);    -   R²⁵ is selected from the group consisting of of H, C₁₋₁₈ alkyl,        preferably C₁₋₄ alkyl; C₃₋₁₀ cycloalkyl, such as C₅₋₁₀        bicycloalkyl; C₃₋₁₀ cycloalkenyl; (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl;        aryl, such as phenyl; 5 or 6 membered heterocyclic ring, such as        pyridyl; alkylaryl, such as benzyl; and each of said C₁₋₁₈        alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl, C₅₋₁₀ bicycloalkyl,        adamantyl, phenyl, pyridyl and benzyl is optionally substituted        with 1-4 of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OH,        oxybenzyl, and OH; and heterocyclic ring having 3 to 7 carbon        atoms, preferably a saturated heterocyclic ring wherein the        heteroatoms are S, S(O), or S(O₂ separated from the        imidazopyridyl ring nitrogen atom by at least 2 heterocyclic        ring carbon atoms. Typically R²⁵ is cyclopentyl or cyclohexyl;    -   R²⁷ is selected from the group consisting of H, C₁₋₁₈ alkyl,        C₃₋₁₀ cycloalkyl, (C₃₋₁₀ cycloalkyl)-C₁₋₆ alkyl; aryl;        arylalkyl, such as benzyl;    -   and pharmaceutical compositions thereof as antiviral drugs.

A further optional embodiment of the present invention relates tocompounds of the formula VI:

or a pharmaceutically acceptable acid addition salt thereof wherein

-   -   R¹ is selected from hydrogen; aryl unsubstituted or substituted        with one or more R⁶, heterocyclic ring unsubstituted or        substituted with one or more R⁶, C₃₋₁₀ cycloalkyl unsubstituted        or substituted with one or more R⁶ and C₄₋₁₀ cycloalkenyl        unsubstituted or substituted with one or more R⁶;    -   Y is selected from the group consisting of a single bond, O;        S(O)_(m); NR¹¹; and a divalent, saturated or unsaturated,        substituted or unsubstituted C₁-C₁₀ hydrocarbon group optionally        including one or more heteroatoms in the main chain, said        heteroatoms being selected from the groups consisting of O, S,        and N; such as C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene,        —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—, —S—(CH₂)₁₋₅—,        —(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—, —(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄—        and C₃₋₁₀ cycloalkylidene;    -   X is selected from the group consisting of a divalent, saturated        or unsaturated, substituted or unsubstituted C₁-C₁₀ hydrocarbon        group optionally including one or more heteroatoms in the main        chain (provided that the heteroatom is not linked to N of the        nucleus), said heteroatoms being selected from the group        consisting of O, S, and N; such as C₁₋₆ alkylene, (for example        —CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂),        —(CH₂)₂₋₄—O—(CH₂)₂₋₄—, —(CH₂)₂₋₄—S—(CH₂)₂₋₄—,        —(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene        (such as —CH═CH—CH₂—), C₂₋₆ alkynylene;    -   m is any integer from 0 to 2;    -   R² is independently selected from the group consisting of        hydrogen C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈        alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio; C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   R³ is selected from the group consisting of aryl; aryloxy;        arylthio; aryl-NR¹⁰—; 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; and each of said aryl,        aryloxy, arylthio, aryl-NR¹⁰—, 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring is optionally        substituted with one or more R¹⁷; C₃₋₁₀ cycloalkyl,        oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenyl with the        proviso that the double bond cannot be adjacent to a nitrogen; H        with the proviso that if X is an alkylene, an alkenylene or an        alkynylene, then X comprises at least 5 carbon atoms;    -   R⁵ is independently selected from the group consisting of        hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈        alkoxy; C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;        haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl; C₃₋₁₀        cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀ cycloalkenyl; C₃₋₁₀        cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring;    -   Each R⁶ and R¹⁷ is independently selected from the group        consisting of hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸;        OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio;        arylalkyl; arylalkyloxy (optionally a oxybenzyl); arylalkylthio        (optionally a benzylthio); 5 or 6 membered heterocyclic,        oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈ hydroxyalkyl;        and each of said aryl, aryloxy, arylthio, arylalkyl,        arylalkyloxy (optionally a oxybenzyl), arylalkylthio (optionally        a benzylthio), 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl is optionally        substituted with 1 or more R¹⁹;    -   Each R⁷ and R⁸ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6 membered heterocyclic ring;        C(═O)R¹²; C(═S)R¹² ; an amino acid residue linked through a        carboxyl group thereof; alternatively, R⁷ and R⁸, together with        the nitrogen to which they are attached, combine to form a 5-6        membered heterocyclic ring;    -   Each R⁹ and R¹⁸ is independently selected from the group        consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl an        amino acid residue linked through an amino group thereof;

Each R¹⁰ and R¹¹ is independently selected from the group the groupconsisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀ cycloalkyl; C₄₋₁₀cycloalkenyl; aryl; C(═O)R¹²; 5-6 membered heterocyclin ring; an aminoacid residue linked through a carboxyl group thereof;

-   -   R¹² is independently selected from the group consisting of H;        C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; an amino acid residue linked through an amino        group thereof;    -   Each R¹³ and R¹⁴ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀        cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═S)R¹²; an amino        acid residue linked through a carboxyl group thereof;    -   Each R¹⁵ and R¹⁶ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl;        aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid        residue linked through a carboxyl group thereof;    -   R¹⁹ is independently selected from the group consisting of H;        C₁₋₁₈ allyl, preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈        alkynyl; C₁₋₁₈ alkoxy, preferably C₁₋₆ alkoxy; C₁₋₁₈ alkylthio;        C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C₄₋₁₀ cycloalkynyl;        halogen; OH; CN; NO₂; NR²⁰R²¹; OCF₃; haloalkyl; C(═O)R²²;        C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆ alkyl); aryl;        aryloxy; arylthio; arylalkyl; and each of said aryl, aryloxy,        arylthio, arylalkyl substituted with 1 or more halogens,        particularly a phenyl substituted with 1-2 halogens;        hydroxyalkyl; 5 or 6 membered heterocyclic, oxyheterocyclic or        thioheterocyclic ring each unsubstituted or substituted with 1        or more halogens;    -   Each R²⁰ and R²¹ is independently selected from the group        consisting of H; C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈        alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀        cycloalkenyl; C(—O)R¹², C(═S)R¹²;    -   R²² is independently selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈        alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴; aryl; C₃₋₁₀ cycloalkyl, ; C₄₋₁₀        cycloalkenyl;    -   Each R²³ and R²⁴ is independently selected from the group the        group consisting of H; C₁₋₁₈ alkyl, preferably C₂₋₃ alkyl,        wherein C₂₋₃ alkyl taken together with N of R²² can form a        saturated heterocycle, which heterocycle is optionally        substituted with OH or aryl or an amino acid residue;    -   Z is selected from (═O), (═S), and (═NR²⁷);    -   R²⁶ is selected from the group consisting of of H, C₁₋₁₈ alkyl,        preferably C₁₋₄ alkyl; C₃₋₁₀ cycloalkyl, such as C₅₋₁₀        bicycloalkyl; C₃₋₁₀ cycloalkenyl; (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl;        aryl, such as phenyl; 5 or 6 membered heterocyclic ring, such as        pyridyl; alkylaryl, such as benzyl; and each of said C₁₋₁₈        alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₁₀        cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl, C₅₋₁₀ bicycloalkyl,        adamantyl, phenyl, pyridyl and benzyl is optionally substituted        with 1-4 of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OH,        oxybenzyl, and OH; and heterocyclic ring having 3 to 7 carbon        atoms, preferably a saturated heterocyclic ring wherein the        heteroatoms are S, S(O), or S(O)₂ separated from the        imidazopyridyl ring nitrogen atom by at least 2 heterocyclic        ring carbon atoms. Typically R²⁶ is cyclopentyl or cyclohexyl;    -   R²⁷ is selected from the group consisting of H, C₁₋₁₈ alkyl,        C₃₋₁₀ cycloalkyl, (C₃₋₁₀ cycloalkyl)-C₁₋₆ alkyl; aryl;        arylalkyl, such as benzyl;    -   and pharmaceutical compositions thereof as antiviral drugs.

The present invention further relates to the use of a compound offormula (Z), optionally of the formula (A), (I), (II), (III), (IV), (V)and (VI) as a medicine, to the use of such compounds in the treatment ofa viral infection or to manufacture a medicament to treat or preventviral infection in a subject. The invention also relates to the use of acompound of formula (Z), optionally of the formula (A), (I), (II),(III), (IV), (V) and (VI) as a pharmaceutically active ingredient,especially as an inhibitor of the viral replication, more preferably asan inhibitor of the replication of a virus of the family of theFlaviviridae or the Picornaviridae, and yet more preferably as aninhibitor of the replication of BVDV, HCV or Coxsackie virus. Therefore,the invention also relates to the use of a compound of formula (Z),optionally of the formula (A), (I), (II), (III), (IV), (V) and (VI) forthe manufacture of a medicine or a pharmaceutical composition havingantiviral activity for the prevention and/or treatment of viralinfections in humans and mammals.

The present invention further relates to a method of treatment of aviral infection in a mammal, including a human, comprising administeringto the mammal in need of such treatment a therapeutically effectiveamount of a compound of formula (Z), more particularly of the formula(A), (I), (II), (III), (IV), (V) and (VI) as an active ingredient,optionally in a mixture with at least a pharmaceutically acceptablecarrier.

The present invention further relates to a composition for separate,combined or sequential use in the treatment or prophylaxis of anti-viralinfections, comprising:

-   -   a) one or more compounds according to the formula (Z) or        optionally formula (A), (I), (II), (III), (IV), (V) and (VI),        and    -   b) one or more compounds effective in the treatment or        prophylaxis of viral infections, including Flaviviral or        Picornaviral enzyme inhibitors; in proportions such as to        provide a synergistic effect in the said treatment of        prophylaxis.

The invention further relates to methods for the preparation ofcompounds of formula (Z), optionally to methods for the preparation ofcompounds of the formula (A), (I), (II), (III), (IV), (V) and (VI) asdetailed above, more particularly to methods for the preparation of thecompounds specifically disclosed herein, to pharmaceutical compositionscomprising them in admixture with at least a pharmaceutically acceptablecarrier, the active ingredient optionally being in a concentration rangeof about 0.1-100% by weight, and to the use of these derivatives namelyas antiviral drugs, more particularly as drugs useful for the treatmentof subjects suffering from HCV, BVDV or Coxsackie virus infection.

The invention also thus to a method for preparing a compound of formula(Z), more particularly of the formula (A), (I), (II), (III), (IV), (V)and (VI) as described herein. Such a methods may essentially comprisethe steps of:

-   -   a) reacting a (substituted) 3,4-diaminopyridine (A) is reacted        with B (Y—R1) to give imidazo[4,5-c]pyridines (C);    -   b) introducing further substituents (R², R⁴ and/or R⁵≠H)        either a) by cylization of an appropriately substituted        3,4-diaminopyridine (A) or b)) by introduction of the        substituent(s) onto the imidazo[4,5-c]pyridine (C);    -   c) reacting the imidazo[4,5-c]pyridines (C) with an alkylating        agent (D) (R³—X—R⁶) in an appropriate solvent under addition of        a base at ambient temperature;    -   optionally, in the case of hydroxy, mercapto or amino        substituents in position 4 or 6 of the imidazopyridine I (Z=O, S        or NR);    -   d) introduction of a further substituent (R²⁵ or R²⁶) at        position 1 or 3 of the imidazo[4,5-c]pyridine.

According to a particular embodiment, the present invention relates tocompounds selected from the following group of compounds, thepharmaceutically acceptable salts, tautomers, and isomers thereof andtheir use in a treatment of viral infection or to manufacture amedicament to treat viral infections:

-   -   2-(2,6-Difluorophenyl)-5-[(2,6-difluorophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-8);    -   5-Benzyl-2-(2,6-difluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-1);    -   5-[(2,6-Difluorophenyl)methyl)-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-3);    -   5-Benzyl-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-4);    -   2-Phenyl-5-(3-phenylpropyl)-5H-imidazo[4,5-c]pyridine (GPJN-14);    -   5-[(2-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-7);    -   5-[(3-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-8);    -   5-[(4-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-9);    -   5-[(2-Methoxyphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-11);    -   5-[(3-Methoxyphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-12);    -   5-[(4-Methoxyphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-13);    -   5-[(4-Methylphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-15);    -   5-[(2-Fluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-17);    -   5-[(3-Fluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-18);    -   5-[(4-Fluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-19);    -   5-[(2-Methylphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-20);    -   5-[(3-Methylphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-21);    -   5-[(4-Bromophenyl)methyl]-2-phenyl-5H-imidazo[4,54-c]pyridine        (GPJN-22)    -   4-[(2-Phenyl-5H-imidazo[4,5-c]pyridin-5-yl)methyl)-benzonitrile        (GPJN-23);    -   2-Phenyl-5-[[4-(trifluoromethyl)phenyl]methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-24);    -   5-[(4-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        hydrochloride (GPJN-9×HCl);    -   5-[(5-Chloro-2-thienyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-25);    -   5-(2-Naphthalenylmethyl)-2-phenyl-5H-imidazo[4,5c-]pyridine        (GPJN-26);    -   2-Phenyl-5-(4-phenylbutyl)-5H-imidazo[4,5-c]pyridine (GPJN-27);    -   5-([1,1′-Biphenyl]-4-ylmethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-32);    -   2-Phenyl-5-(1-phenylethyl)-5H-imidazo[4,5-c]pyridine (GPJN-33);    -   5-(1-Naphthalenylmethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-36);    -   2-(2,6-Difluorophenyl)-5-[(2,4-difluorophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-40);    -   5-[(4-Bromophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-52);    -   5-[(4-Bromophenyl)methyl]-2-(2-chlorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-54);    -   5-[(4-Bromophenyl)methyl]-2-(3-chlorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-55);    -   5-[(4-Bromophenyl)methyl]-2-(4-chlorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-56);    -   5-[(4-Bromophenyl)methyl]-2-(2-pyridinyl)-5H-imidazo[4,5-c)pyridine        (GPJN-58);    -   5-[(4-Bromophenyl)methyl]-2-(2-thienyl)-5H-imidazo[4,5-c]pyridine        (GPJN-53);    -   5-[(4-Bromophenyl)methyl]-2-(1-naphthalenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-62);    -   5-[(4-Bromophenyl)methyl]-2-(2-naphthalenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-63);    -   5-[(4-Iodophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-68);    -   5-[(4-Bromophenyl)methyl]-2-(3-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-50);    -   5-[(4-Bromophenyl)methyl]-2-(3-methylphenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-60);    -   5-[(4-Bromophenyl)methyl]-2-(3-methoxyphenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-64);    -   5-[(4-Bromophenyl)methyl]-2-(3-bromophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-65);    -   5-[(4-Chlorophenyl)methyl]-2-(3-bromophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-80);    -   5-[(4-Chlorophenyl)methyl]-2-(3-chlorophenyl)-5H-imidazo[4,5-c]pyridine;    -   5-(2-Phenoxy-ethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-73);    -   5-(3-Phenyl-prop-2-en-1-yl)-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-75);    -   2-(3-Bromophenyl)-5-[(4-iodophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-79);    -   5-[(4-Bromophenyl)methyl]-2-[(phenylthio)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-83);    -   5-[(4-Bromophenyl)methyl]-2-[3-(trifluoromethyl)phenyl]-5H-imidazo[4,5-c]pyridine        (GPJN-87);    -   5-([1,1′-Biphenyl]-4-ylmethyl)-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-110);    -   5-[(4-Chlorophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-112);    -   2-(2-Fluorophenyl)-5-[(4-iodophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-113);    -   5-[[4-(1,1-Dimethylethyl)phenyl]methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-114);

Optionally, the present invention relates to compounds selected from thefollowing group of compounds, the pharmaceutically acceptable salts,tautomers, and isomers thereof and their use in a treatment of viralinfection, more particularly for the treatment of HCV infection, or tomanufacture a medicament to treat viral infections, more particularlyHCV infections:

-   -   5-[(4-Bromophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-52);    -   5-[(4-Bromophenyl)methyl]-2-(2-pyridinyl)-5H-imidazo[4,5-c]pyridine        (GPJN-58);    -   5-[(4-Bromophenyl)methyl]-2-[(phenylthio)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-83);    -   5-[(4-Bromophenyl)methyl]-2-[3-(trifluoromethyl)phenyl]-5H-imidazo[4,5-c]pyridine        (GPJN-87);    -   5-([1,1′-Biphenyl]-4-ylmethyl)-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-110);    -   5-[(4-Chlorophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-112);    -   2-(2-Fluorophenyl)-5-[(4-iodophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-113);    -   5-[[4-(1,1-Dimethylethyl)phenyl]methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-114).

The invention further relates to methods of screening antiviralcompounds which comprises a) providing a compounds of the formula (Z),or optionally of the formula (A), (I), (II), (III), (IV), (V) or (VI)and b) determining the anti-viral activity of said compound.

Exemplary Enumerated Compounds.

By way of example and not limitation, embodiments of the invention arenamed below in tabular format (Table 7). Each embodiment of Table 7 isdepicted as a substituted nucleus (Sc) in which the nucleus isdesignated by a number and each substituent is designated in order byfurther numbers. Table 1 is a schedule of nuclei used in forming theembodiments of Table 7. Each nucleus (Sc) is given a number designationfrom Table 1, and this designation appears first in each embodimentname. Similarly, Tables 2, 3, 4, 5 and 6 list the selected substituents,again by number designation.

Accordingly, each named embodiment of Table 7 is depicted by a numberdesignating the nucleus from Table 1. If the nucleus is of formula 1(from Table 1), then the letter and number substituents are in the orderR¹ (Table 2), R³ (Table 3), R⁴(Table 4), and X (Table 6). If the nucleusis of formula 2 (from Table 1), then the letter and number substituentsare in the order R¹ (Table 2), R³ (Table 3), R⁴ (Table 4), R²⁶ (Table5), and X (Table 6). The same embodiments of the invention exist for thenucleus of formula 2 (Table 1) wherein the N at position 1 issubstituted by R²⁵ (corresponding to the embodiments of R²⁶ of Table 5)and the single or double bonds in the imidazo pyridine ring are adjustedaccordingly.

Each group is shown having one or more tildas (“˜”). The tildas are thepoints of covalent attachment of the group. TABLE 1

TABLE 2 R¹ Substituents

TABLE 3 R³ Substituents

TABLE 4 R⁴ Substituents

TABLE 5 R²⁶ Substituents

TABLE 6 X Substituents

TABLE 7 Selected Embodiments of the Invention Embodiments of Formula 11.1.1.1.1; 1.1.1.1.2; 1.1.1.1.3; 1.1.1.2.1; 1.1.1.2.2; 1.1.1.2.3;1.1.2.1.1; 1.1.2.1.2; 1.1.2.1.3; 1.1.2.2.1; 1.1.2.2.2; 1.1.2.2.3;1.1.3.1.1; 1.1.3.1.2; 1.1.3.1.3; 1.1.3.2.1; 1.1.3.2.2; 1.1.3.2.3;1.1.4.1.1; 1.1.4.1.2; 1.1.4.1.3; 1.1.4.2.1; 1.1.4.2.2; 1.1.4.2.3;1.1.5.1.1; 1.1.5.1.2; 1.1.5.1.3; 1.1.5.2.1; 1.1.5.2.2; 1.1.5.2.3;1.1.6.1.1; 1.1.6.1.2; 1.1.6.1.3; 1.1.6.2.1; 1.1.6.2.2; 1.1.6.2.3;1.2.1.1.1; 1.2.1.1.2; 1.2.1.1.3; 1.2.1.2.1; 1.2.1.2.2; 1.2.1.2.3;1.2.2.1.1; 1.2.2.1.2; 1.2.2.1.3; 1.2.2.2.1; 1.2.2.2.2; 1.2.2.2.3;1.2.3.1.1; 1.2.3.1.2; 1.2.3.1.3; 1.2.3.2.1; 1.2.3.2.2; 1.2.3.2.3;1.2.4.1.1; 1.2.4.1.2; 1.2.4.1.3; 1.2.4.2.1; 1.2.4.2.2; 1.2.4.2.3;1.2.5.1.1; 1.2.5.1.2; 1.2.5.1.3; 1.2.5.2.1; 1.2.5.2.2; 1.2.5.2.3;1.2.6.1.1; 1.2.6.1.2; 1.2.6.1.3; 1.2.6.2.1; 1.2.6.2.2; 1.2.6.2.3;1.3.1.1.1; 1.3.1.1.2; 1.3.1.1.3; 1.3.1.2.1; 1.3.1.2.2; 1.3.1.2.3;1.3.2.1.1; 1.3.2.1.2; 1.3.2.1.3; 1.3.2.2.1; 1.3.2.2.2; 1.3.2.2.3;1.3.3.1.1; 1.3.3.1.2; 1.3.3.1.3; 1.3.3.2.1; 1.3.3.2.2; 1.3.3.2.3;1.3.4.1.1; 1.3.4.1.2; 1.3.4.1.3; 1.3.4.2.1; 1.3.4.2.2; 1.3.4.2.3;1.3.5.1.1; 1.3.5.1.2; 1.3.5.1.3; 1.3.5.2.1; 1.3.5.2.2; 1.3.5.2.3;1.3.6.1.1; 1.3.6.1.2; 1.3.6.1.3; 1.3.6.2.1; 1.3.6.2.2; 1.3.6.2.3;1.4.1.1.1; 1.4.1.1.2; 1.4.1.1.3; 1.4.1.2.1; 1.4.1.2.2; 1.4.1.2.3;1.4.2.1.1; 1.4.2.1.2; 1.4.2.1.3; 1.4.2.2.1; 1.4.2.2.2; 1.4.2.2.3;1.4.3.1.1; 1.4.3.1.2; 1.4.3.1.3; 1.4.3.2.1; 1.4.3.2.2; 1.4.3.2.3;1.4.4.1.1; 1.4.4.1.2; 1.4.4.1.3; 1.4.4.2.1; 1.4.4.2.2; 1.4.4.2.3;1.4.5.1.1; 1.4.5.1.2; 1.4.5.1.3; 1.4.5.2.1; 1.4.5.2.2; 1.4.5.2.3;1.4.6.1.1; 1.4.6.1.2; 1.4.6.1.3; 1.4.6.2.1; 1.4.6.2.2; 1.4.6.2.3;1.5.1.1.1; 1.5.1.1.2; 1.5.1.1.3; 1.5.1.2.1; 1.5.1.2.2; 1.5.1.2.3;1.5.2.1.1; 1.5.2.1.2; 1.5.2.1.3; 1.5.2.2.1; 1.5.2.2.2; 1.5.2.2.3;1.5.3.1.1; 1.5.3.1.2; 1.5.3.1.3; 1.5.3.2.1; 1.5.3.2.2; 1.5.3.2.3;1.5.4.1.1; 1.5.4.1.2; 1.5.4.1.3; 1.5.4.2.1; 1.5.4.2.2; 1.5.4.2.3;1.5.5.1.1; 1.5.5.1.2; 1.5.5.1.3; 1.5.5.2.1; 1.5.5.2.2; 1.5.5.2.3;1.5.6.1.1; 1.5.6.1.2; 1.5.6.1.3; 1.5.6.2.1; 1.5.6.2.2; 1.5.6.2.3;1.6.1.1.1; 1.6.1.1.2; 1.6.1.1.3; 1.6.1.2.1; 1.6.1.2.2; 1.6.1.2.3;1.6.2.1.1; 1.6.2.1.2; 1.6.2.1.3; 1.6.2.2.1; 1.6.2.2.2; 1.6.2.2.3;1.6.3.1.1; 1.6.3.1.2; 1.6.3.1.3; 1.6.3.2.1; 1.6.3.2.2; 1.6.3.2.3;1.6.4.1.1; 1.6.4.1.2; 1.6.4.1.3; 1.6.4.2.1; 1.6.4.2.2; 1.6.4.2.3;1.6.5.1.1; 1.6.5.1.2; 1.6.5.1.3; 1.6.5.2.1; 1.6.5.2.2; 1.6.5.2.3;1.6.6.1.1; 1.6.6.1.2; 1.6.6.1.3; 1.6.6.2.1; 1.6.6.2.2; 1.6.6.2.3;1.7.1.1.1; 1.7.1.1.2; 1.7.1.1.3; 1.7.1.2.1; 1.7.1.2.2; 1.7.1.2.3;1.7.2.1.1; 1.7.2.1.2; 1.7.2.1.3; 1.7.2.2.1; 1.7.2.2.2; 1.7.2.2.3;1.7.3.1.1; 1.7.3.1.2; 1.7.3.1.3; 1.7.3.2.1; 1.7.3.2.2; 1.7.3.2.3;1.7.4.1.1; 1.7.4.1.2; 1.7.4.1.3; 1.7.4.2.1; 1.7.4.2.2; 1.7.4.2.3;1.7.5.1.1; 1.7.5.1.2; 1.7.5.1.3; 1.7.5.2.1; 1.7.5.2.2; 1.7.5.2.3;1.7.6.1.1; 1.7.6.1.2; 1.7.6.1.3; 1.7.6.2.1; 1.7.6.2.2; 1.7.6.2.3.Embodiments of Formula 2 2.1.1.1.1.1; 2.1.1.1.1.2; 2.1.1.1.1.3;2.1.1.1.2.1; 2.1.1.1.2.2; 2.1.1.1.2.3; 2.1.1.2.1.1; 2.1.1.2.1.2;2.1.1.2.1.3; 2.1.1.2.2.1; 2.1.1.2.2.2; 2.1.1.2.2.3; 2.1.2.1.1.1;2.1.2.1.1.2; 2.1.2.1.1.3; 2.1.2.1.2.1; 2.1.2.1.2.2; 2.1.2.1.2.3;2.1.2.2.1.1; 2.1.2.2.1.2; 2.1.2.2.1.3; 2.1.2.2.2.1; 2.1.2.2.2.2;2.1.2.2.2.3; 2.1.3.1.1.1; 2.1.3.1.1.2; 2.1.3.1.1.3; 2.1.3.1.2.1;2.1.3.1.2.2; 2.1.3.1.2.3; 2.1.3.2.1.1; 2.1.3.2.1.2; 2.1.3.2.1.3;2.1.3.2.2.1; 2.1.3.2.2.2; 2.1.3.2.2.3; 2.1.4.1.1.1; 2.1.4.1.1.2;2.1.4.1.1.3; 2.1.4.1.2.1; 2.1.4.1.2.2; 2.1.4.1.2.3; 2.1.4.2.1.1;2.1.4.2.1.2; 2.1.4.2.1.3; 2.1.4.2.2.1; 2.1.4.2.2.2; 2.1.4.2.2.3;2.1.5.1.1.1; 2.1.5.1.1.2; 2.1.5.1.1.3; 2.1.5.1.2.1; 2.1.5.1.2.2;2.1.5.1.2.3; 2.1.5.2.1.1; 2.1.5.2.1.2; 2.1.5.2.1.3; 2.1.5.2.2.1;2.1.5.2.2.2; 2.1.5.2.2.3; 2.1.6.1.1.1; 2.1.6.1.1.2; 2.1.6.1.1.3;2.1.6.1.2.1; 2.1.6.1.2.2; 2.1.6.1.2.3; 2.1.6.2.1.1; 2.1.6.2.1.2;2.1.6.2.1.3; 2.1.6.2.2.1; 2.1.6.2.2.2; 2.1.6.2.2.3; 2.2.1.1.1.1;2.2.1.1.1.2; 2.2.1.1.1.3; 2.2.1.1.2.1; 2.2.1.1.2.2; 2.2.1.1.2.3;2.2.1.2.1.1; 2.2.1.2.1.2; 2.2.1.2.1.3; 2.2.1.2.2.1; 2.2.1.2.2.2;2.2.1.2.2.3; 2.2.2.1.1.1; 2.2.2.1.1.2; 2.2.2.1.1.3; 2.2.2.1.2.1;2.2.2.1.2.2; 2.2.2.1.2.3; 2.2.2.2.1.1; 2.2.2.2.1.2; 2.2.2.2.1.3;2.2.2.2.2.1; 2.2.2.2.2.2; 2.2.2.2.2.3; 2.2.3.1.1.1; 2.2.3.1.1.2;2.2.3.1.1.3; 2.2.3.1.2.1; 2.2.3.1.2.2; 2.2.3.1.2.3; 2.2.3.2.1.1;2.2.3.2.1.2; 2.2.3.2.1.3; 2.2.3.2.2.1; 2.2.3.2.2.2; 2.2.3.2.2.3;2.2.4.1.1.1; 2.2.4.1.1.2; 2.2.4.1.1.3; 2.2.4.1.2.1; 2.2.4.1.2.2;2.2.4.1.2.3; 2.2.4.2.1.1; 2.2.4.2.1.2; 2.2.4.2.1.3; 2.2.4.2.2.1;2.2.4.2.2.2; 2.2.4.2.2.3; 2.2.5.1.1.1; 2.2.5.1.1.2; 2.2.5.1.1.3;2.2.5.1.2.1; 2.2.5.1.2.2; 2.2.5.1.2.3; 2.2.5.2.1.1; 2.2.5.2.1.2;2.2.5.2.1.3; 2.2.5.2.2.1; 2.2.5.2.2.2; 2.2.5.2.2.3; 2.2.6.1.1.1;2.2.6.1.1.2; 2.2.6.1.1.3; 2.2.6.1.2.1; 2.2.6.1.2.2; 2.2.6.1.2.3;2.2.6.2.1.1; 2.2.6.2.1.2; 2.2.6.2.1.3; 2.2.6.2.2.1; 2.2.6.2.2.2;2.2.6.2.2.3; 2.3.1.1.1.1; 2.3.1.1.1.2; 2.3.1.1.1.3; 2.3.1.1.2.1;2.3.1.1.2.2; 2.3.1.1.2.3; 2.3.1.2.1.1; 2.3.1.2.1.2; 2.3.1.2.1.3;2.3.1.2.2.1; 2.3.1.2.2.2; 2.3.1.2.2.3; 2.3.2.1.1.1; 2.3.2.1.1.2;2.3.2.1.1.3; 2.3.2.1.2.1; 2.3.2.1.2.2; 2.3.2.1.2.3; 2.3.2.2.1.1;2.3.2.2.1.2; 2.3.2.2.1.3; 2.3.2.2.2.1; 2.3.2.2.2.2; 2.3.2.2.2.3;2.3.3.1.1.1; 2.3.3.1.1.2; 2.3.3.1.1.3; 2.3.3.1.2.1; 2.3.3.1.2.2;2.3.3.1.2.3; 2.3.3.2.1.1; 2.3.3.2.1.2; 2.3.3.2.1.3; 2.3.3.2.2.1;2.3.3.2.2.2; 2.3.3.2.2.3; 2.3.4.1.1.1; 2.3.4.1.1.2; 2.3.4.1.1.3;2.3.4.1.2.1; 2.3.4.1.2.2; 2.3.4.1.2.3; 2.3.4.2.1.1; 2.3.4.2.1.2;2.3.4.2.1.3; 2.3.4.2.2.1; 2.3.4.2.2.2; 2.3.4.2.2.3; 2.3.5.1.1.1;2.3.5.1.1.2; 2.3.5.1.1.3; 2.3.5.1.2.1; 2.3.5.1.2.2; 2.3.5.1.2.3;2.3.5.2.1.1; 2.3.5.2.1.2; 2.3.5.2.1.3; 2.3.5.2.2.1; 2.3.5.2.2.2;2.3.5.2.2.3; 2.3.6.1.1.1; 2.3.6.1.1.2; 2.3.6.1.1.3; 2.3.6.1.2.1;2.3.6.1.2.2; 2.3.6.1.2.3; 2.3.6.2.1.1; 2.3.6.2.1.2; 2.3.6.2.1.3;2.3.6.2.2.1; 2.3.6.2.2.2; 2.3.6.2.2.3; 2.4.1.1.1.1; 2.4.1.1.1.2;2.4.1.1.1.3; 2.4.1.1.2.1; 2.4.1.1.2.2; 2.4.1.1.2.3; 2.4.1.2.1.1;2.4.1.2.1.2; 2.4.1.2.1.3; 2.4.1.2.2.1; 2.4.1.2.2.2; 2.4.1.2.2.3;2.4.2.1.1.1; 2.4.2.1.1.2; 2.4.2.1.1.3; 2.4.2.1.2.1; 2.4.2.1.2.2;2.4.2.1.2.3; 2.4.2.2.1.1; 2.4.2.2.1.2; 2.4.2.2.1.3; 2.4.2.2.2.1;2.4.2.2.2.2; 2.4.2.2.2.3; 2.4.3.1.1.1; 2.4.3.1.1.2; 2.4.3.1.1.3;2.4.3.1.2.1; 2.4.3.1.2.2; 2.4.3.1.2.3; 2.4.3.2.1.1; 2.4.3.2.1.2;2.4.3.2.1.3; 2.4.3.2.2.1; 2.4.3.2.2.2; 2.4.3.2.2.3; 2.4.4.1.1.1;2.4.4.1.1.2; 2.4.4.1.1.3; 2.4.4.1.2.1; 2.4.4.1.2.2; 2.4.4.1.2.3;2.4.4.2.1.1; 2.4.4.2.1.2; 2.4.4.2.1.3; 2.4.4.2.2.1; 2.4.4.2.2.2;2.4.4.2.2.3; 2.4.5.1.1.1; 2.4.5.1.1.2; 2.4.5.1.1.3; 2.4.5.1.2.1;2.4.5.1.2.2; 2.4.5.1.2.3; 2.4.5.2.1.1; 2.4.5.2.1.2; 2.4.5.2.1.3;2.4.5.2.2.1; 2.4.5.2.2.2; 2.4.5.2.2.3; 2.4.6.1.1.1; 2.4.6.1.1.2;2.4.6.1.1.3; 2.4.6.1.2.1; 2.4.6.1.2.2; 2.4.6.1.2.3; 2.4.6.2.1.1;2.4.6.2.1.2; 2.4.6.2.1.3; 2.4.6.2.2.1; 2.4.6.2.2.2; 2.4.6.2.2.3;2.5.1.1.1.1; 2.5.1.1.1.2; 2.5.1.1.1.3; 2.5.1.1.2.1; 2.5.1.1.2.2;2.5.1.1.2.3; 2.5.1.2.1.1; 2.5.1.2.1.2; 2.5.1.2.1.3; 2.5.1.2.2.1;2.5.1.2.2.2; 2.5.1.2.2.3; 2.5.2.1.1.1; 2.5.2.1.1.2; 2.5.2.1.1.3;2.5.2.1.2.1; 2.5.2.1.2.2; 2.5.2.1.2.3; 2.5.2.2.1.1; 2.5.2.2.1.2;2.5.2.2.1.3; 2.5.2.2.2.1; 2.5.2.2.2.2; 2.5.2.2.2.3; 2.5.3.1.1.1;2.5.3.1.1.2; 2.5.3.1.1.3; 2.5.3.1.2.1; 2.5.3.1.2.2; 2.5.3.1.2.3;2.5.3.2.1.1; 2.5.3.2.1.2; 2.5.3.2.1.3; 2.5.3.2.2.1; 2.5.3.2.2.2;2.5.3.2.2.3; 2.5.4.1.1.1; 2.5.4.1.1.2; 2.5.4.1.1.3; 2.5.4.1.2.1;2.5.4.1.2.2; 2.5.4.1.2.3; 2.5.4.2.1.1; 2.5.4.2.1.2; 2.5.4.2.1.3;2.5.4.2.2.1; 2.5.4.2.2.2; 2.5.4.2.2.3; 2.5.5.1.1.1; 2.5.5.1.1.2;2.5.5.1.1.3; 2.5.5.1.2.1; 2.5.5.1.2.2; 2.5.5.1.2.3; 2.5.5.2.1.1;2.5.5.2.1.2; 2.5.5.2.1.3; 2.5.5.2.2.1; 2.5.5.2.2.2; 2.5.5.2.2.3;2.5.6.1.1.1; 2.5.6.1.1.2; 2.5.6.1.1.3; 2.5.6.1.2.1; 2.5.6.1.2.2;2.5.6.1.2.3; 2.5.6.2.1.1; 2.5.6.2.1.2; 2.5.6.2.1.3; 2.5.6.2.2.1;2.5.6.2.2.2; 2.5.6.2.2.3; 2.6.1.1.1.1; 2.6.1.1.1.2; 2.6.1.1.1.3;2.6.1.1.2.1; 2.6.1.1.2.2; 2.6.1.1.2.3; 2.6.1.2.1.1; 2.6.1.2.1.2;2.6.1.2.1.3; 2.6.1.2.2.1; 2.6.1.2.2.2; 2.6.1.2.2.3; 2.6.2.1.1.1;2.6.2.1.1.2; 2.6.2.1.1.3; 2.6.2.1.2.1; 2.6.2.1.2.2; 2.6.2.1.2.3;2.6.2.2.1.1; 2.6.2.2.1.2; 2.6.2.2.1.3; 2.6.2.2.2.1; 2.6.2.2.2.2;2.6.2.2.2.3; 2.6.3.1.1.1; 2.6.3.1.1.2; 2.6.3.1.1.3; 2.6.3.1.2.1;2.6.3.1.2.2; 2.6.3.1.2.3; 2.6.3.2.1.1; 2.6.3.2.1.2; 2.6.3.2.1.3;2.6.3.2.2.1; 2.6.3.2.2.2; 2.6.3.2.2.3; 2.6.4.1.1.1; 2.6.4.1.1.2;2.6.4.1.1.3; 2.6.4.1.2.1; 2.6.4.1.2.2; 2.6.4.1.2.3; 2.6.4.2.1.1;2.6.4.2.1.2; 2.6.4.2.1.3; 2.6.4.2.2.1; 2.6.4.2.2.2; 2.6.4.2.2.3;2.6.5.1.1.1; 2.6.5.1.1.2; 2.6.5.1.1.3; 2.6.5.1.2.1; 2.6.5.1.2.2;2.6.5.1.2.3; 2.6.5.2.1.1; 2.6.5.2.1.2; 2.6.5.2.1.3; 2.6.5.2.2.1;2.6.5.2.2.2; 2.6.5.2.2.3; 2.6.6.1.1.1; 2.6.6.1.1.2; 2.6.6.1.1.3;2.6.6.1.2.1; 2.6.6.1.2.2; 2.6.6.1.2.3; 2.6.6.2.1.1; 2.6.6.2.1.2;2.6.6.2.1.3; 2.6.6.2.2.1; 2.6.6.2.2.2; 2.6.6.2.2.3; 2.7.1.1.1.1;2.7.1.1.1.2; 2.7.1.1.1.3; 2.7.1.1.2.1; 2.7.1.1.2.2; 2.7.1.1.2.3;2.7.1.2.1.1; 2.7.1.2.1.2; 2.7.1.2.1.3; 2.7.1.2.2.1; 2.7.1.2.2.2;2.7.1.2.2.3; 2.7.2.1.1.1; 2.7.2.1.1.2; 2.7.2.1.1.3; 2.7.2.1.2.1;2.7.2.1.2.2; 2.7.2.1.2.3; 2.7.2.2.1.1; 2.7.2.2.1.2; 2.7.2.2.1.3;2.7.2.2.2.1; 2.7.2.2.2.2; 2.7.2.2.2.3; 2.7.3.1.1.1; 2.7.3.1.1.2;2.7.3.1.1.3; 2.7.3.1.2.1; 2.7.3.1.2.2; 2.7.3.1.2.3; 2.7.3.2.1.1;2.7.3.2.1.2; 2.7.3.2.1.3; 2.7.3.2.2.1; 2.7.3.2.2.2; 2.7.3.2.2.3;2.7.4.1.1.1; 2.7.4.1.1.2; 2.7.4.1.1.3; 2.7.4.1.2.1; 2.7.4.1.2.2;2.7.4.1.2.3; 2.7.4.2.1.1; 2.7.4.2.1.2; 2.7.4.2.1.3; 2.7.4.2.2.1;2.7.4.2.2.2; 2.7.4.2.2.3; 2.7.5.1.1.1; 2.7.5.1.1.2; 2.7.5.1.1.3;2.7.5.1.2.1; 2.7.5.1.2.2; 2.7.5.1.2.3; 2.7.5.2.1.1; 2.7.5.2.1.2;2.7.5.2.1.3; 2.7.5.2.2.1; 2.7.5.2.2.2; 2.7.5.2.2.3; 2.7.6.1.1.1;2.7.6.1.1.2; 2.7.6.1.1.3; 2.7.6.1.2.1; 2.7.6.1.2.2; 2.7.6.1.2.3;2.7.6.2.1.1; 2.7.6.2.1.2; 2.7.6.2.1.3; 2.7.6.2.2.1; 2.7.6.2.2.2;2.7.6.2.2.3.

DETAILED DESCRIPTION

In each of the following definitions, the number of carbon atomsrepresents the maximum number of carbon atoms generally optimallypresent in the substituent or linker; it is understood that whereotherwise indicated in the present application, the number of carbon ISatoms represents the optimal maximum number of carbon atoms for thatparticular substituent or linker.

The term “C₁₋₁₈ alkyl” as used herein C1-C18 normal, secondary, ortertiary hydrocarbon. Examples are methyl, ethyl, 1-propyl, 2-propyl,1-butyl, 2-methyl-1-propyl(i-Bu), 2-butyl (s-Bu) 2-methyl-2-propyl(t-Bu), 1-pentyl (n-pentyl), 2-pentyl, 3-pentyl, 2-methyl-2-butyl,3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl,3hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl,3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl,3,3-dimethyl-2-butyl, cyclopropyl, cyclobutyl, cyclopentyl andcyclohexyl. The term also includes C₁₋₁₈ halo-alkyls, which is a C₁₋₁₈alkyl bearing at least one halogen.

As used herein and unless otherwise stated, the term “C₃₋₁₀ cycloalkyl”means a monocyclic saturated hydrocarbon monovalent radical having from3 to 10 carbon atoms, such as for instance cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like, or aC₇₋₁₀ polycyclic saturated hydrocarbon monovalent radical having from 7to 10 carbon atoms such as, for instance, norbornyl, fenchyl,trimethyltricycloheptyl or adamantyl.

As used herein and unless otherwise stated, the term “C₃₋₁₀cycloalkylene” refers to a cyclic hydrocarbon radical of 3-10 carbonatoms, and having two monovalent radical centers derived by the removalof two hydrogen atoms from the same or two different carbon atoms of aparent alkane; i.e. the divalent hydrocarbon radical corresponding tothe above defined C₃₋₁₀ cycloalkyl.

The terms “C₂₋₁₈ alkenyl” and “C₃₋₁₀ cycloalkenyl” as used herein isC2-C18 normal, secondary or tertiary and respectively C3-10 cyclichydrocarbon with at least one site (usually 1 to 3, preferably 1) ofunsaturation, i.e. a carbon-carbon, sp2 double bond. Examples include,but are not limited to: ethylene or vinyl (—CH═CH2), allyl (—CH2CH═CH2),cyclopentenyl (—C5H7), and 5-hexenyl (—CH2 CH2CH2CH2CH═CH2). The doublebond may be in the cis or trans configuration.

The terms “C₂₋₁₈ alkynyl” and “C₃₋₁₀ cycloalkynyl” as used herein referrespectively C2-C18 normal, secondary, tertiary or the C3-10 cyclichydrocarbon with at least one site (usually 1 to 3, preferably 1) ofunsaturation, i.e. a carbon-carbon, sp triple bond. Examples include,but are not limited to: acetylenic (—CO°CH) and propargyl (—CH2C°CH).

The terms “C₁₋₁₈ alkylene” as used herein each refer to a saturated,branched or straight chain hydrocarbon radical of 1-18 carbon atoms, andhaving two monovalent radical centers derived by the removal of twohydrogen atoms from the same or two different carbon atoms of a parentalkane. Typical alkylene radicals include, but are not limited to:methylene (—CH2-) 1,2-ethyl (—CH2CH2-), 1,3-propyl (—CH2CH2CH2-),1,4-butyl (—CH2CH2CH2CH2-), and the like.

The terms “C₂₋₁₈ alkenylene” and “C₃₋₁₀ cycloalkenylene as used hereinrefer to an unsaturated branched chain, straight chain, and respectivelya cyclic hydrocarbon radical of 2-18 respectively 3-10 carbon atoms, andhaving two monovalent radical centers derived by the removal of twohydrogen atoms from the same or two different carbon atoms of a parentalkene, i.e. double carbon-carbon bond moiety. Typical alkenyleneradicals include, but are not limited to: 1,2-ethylene (—CH═CH—).

The terms “C₂₋₁₈ alkynylene” and “C₃₋₁₀ cycloalkenylene” as used hereinrefer respectively to an unsaturated, branched or straight chain of 2-18carbon atoms or to a cyclic hydrocarbon radical of 3-10 carbon atomsrespectively, having two monovalent radical centers derived by theremoval of two hydrogen atoms from the same or two different carbonatoms of a parent alkane, i.e. triple carbon-carbon bond moiety. Typicalalkynylene radicals include, but are not limited to: acetylene (—C°C—),propargyl (—CH2C°C—), and 4-pentynyl (—CH2CH2CH2C°CH—).

The term “aryl” as used herein means a aromatic hydrocarbon radical of6-20 carbon atoms derived by the removal of hydrogen from a carbon atomof a parent aromatic ring system. Typical aryl groups include, but arenot limited to 1 ring, or 2 or 3 rings fused together, radicals derivedfrom benzene, naphthalene, spiro, anthracene, biphenyl, and the like.

“Arylalkyl” as used herein refers to an alkyl radical in which one ofthe hydrogen atoms bonded to a carbon atom, typically a terminal or sp3carbon atom, is replaced with an aryl radical. Typical arylalkyl groupsinclude, but are not limited to, benzyl, 2-phenylethan-1-yl,2-phenylethen-1-yl, naphthylmethyl, 2-naphthylethan-1-yl,2-naphthylethen-1-yl, naphthobenzyl, 2-naphthophenylethan-1-yl and thelike. The arylalkyl group comprises 6 to 20 carbon atoms, e.g. the alkylmoiety, including alkanyl, alkenyl or alkynyl groups, of the arylalkylgroup is 1 to 6 carbon atoms and the aryl moiety is 5 to 14 carbonatoms.

The term “heterocyclic ring” as used herein means pyridyl,dihydroypyridyl, tetrahydropyridyl (piperidyl), thiazolyl,tetrahydrothiophenyl, sulfur oxidized tetrahydrothiophenyl, furanyl,thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl,thianaphthalenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl,benzimidazolyl, piperidinyl, 4-piperidonyl, pyrrolidinyl,2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, bis-tetrahydrofuranyl,tetrahydropyranyl, bis-tetrahydropyranyl, tetrahydroquinolinyl,tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl,azocinyl, triazinyl, 6H-1,2,5-thiadiazinyl, 2H,6H-1,5,2-dithiazinyl,thianthrenyl, pyranyl, isobenzofuranyl, chromenyl, xanthenyl,phenoxathinyl, 2H-pyrrolyl, isothiazolyl, isoxazolyl, pyrazinyl,pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, 1H-indazoly, purinyl,4H-quinolizinyl, phthalazinyl, naphthyridinyl, quinoxalinyl,quinazolinyl, cinnolinyl, pteridinyl, 4a-carbazolyl, carbazolyl,β-carbolinyl, phenanthridinyl, acridinyl, pyrimidinyl, phenantbrolinyl,phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl,chromanyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl,piperazinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl,oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl,benzothienyl, benzothiazolyl and isatinoyl.

Heteroaryl means pyridyl, dihydropyridyl, pyridazinyl, pyrimidinyl,pyrazinyl, s-triazinyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl,pyrazolyl, isothiazolyl, furanyl, thiofuranyl, thienyl, and pyrrolyl.

By way of example, carbon bonded heterocyclic rings are bonded atposition 2, 3, 4, 5, or 6 of a pyridine, position 3, 4, 5, or 6 of apyridazine, position 2, 4, 5, or 6 of a pyrimidine, position 2, 3, 5, or6 of a pyrazoline, position 2, 3, 4, or 5 of a furan, tetrahydrofuran,thiofuran, thiophene, pyrrole or tetrahydropyrrole, position 2, 4, or 5of an oxazole, imidazole or thiazole, position 3, 4, or 5 of anisoxazole, pyrazole, or isothiazole, position 2 or 3 of an aziridine,position 2, 3, or 4 of an azetidine, position 2, 3, 4, 5, 6, 7, or 8 ofa quinoline or position 1, 3, 4, 5, 6, 7, or 8 of an isoquinoline. Stillmore typically, carbon bonded heterocycles include 2-pyridyl, 3-pyridyl,4-pyridyl, 5-pyridyl, 6-pyridyl, 3-pyridazinyl, 4-pyridazinyl,5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl,5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl,6-pyrazinyl, 2-thiazolyl, 4thiazolyl, or 5-thiazolyl.

By way of example, nitrogen bonded heterocyclic rings are bonded atposition 1 of an aziridine, azetidine, pyrrole, pyrrolidine,2-pyrroline, 3-pyrroline, imidazole, imidazolidine, 2-imidazoline,3-imidazoline, pyrazole, pyrazoline, 2-pyrazoline, 3-pyrazoline,piperidine, piperazine, indole, indoline, 1H-indazole, position 2 of aisoindole, or isoindoline, position 4 of a morpholine, and position 9 ofa carbazole, or β-carboline. Still more typically, nitrogen bondedheterocycles include 1-aziridyl, 1-azetedyl, 1-pyrrolyl, 1-imidazolyl,1-pyrazolyl, and 1-piperidinyl.

“Carbocycle” means a saturated, unsaturated or aromatic ring systemhaving 3 to 7 carbon atoms as a monocycle or 7 to 12 carbon atoms as abicycle. Monocyclic carbocycles have 3 to 6 ring atoms, still moretypically 5 or 6 ring atoms. Bicyclic carbocycles have 7 to 12 ringatoms, e.g. arranged as a bicyclo [4,5], [5,5], [5,6] or [6,6] system,or 9 or 10 ring atoms arranged as a bicyclo [5,6] or [6,6] system.Examples of monocyclic carbocycles include cyclopropyl, cyclobutyl,cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl,cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, 1-cyclohex-3-enyl,phenyl, spiryl and naphthyl. Carbocycle thus includes some aryl groups.

As used herein and unless otherwise stated, the terms “C₁₋₁₈ alkoxy”,“C₃₋₁₀ cycloalkoxy”, “aryloxy”, “arylalkyloxy”, “oxyheterocyclic ring”,“thio C₁₋₇ alkyl”, thio C₃₋₁₀ cycloalkyl”, “arylthio”, “arylalkylthio”and “thioheterocyclic ring” refer to substituents wherein a C₁₋₁₈ alkylradical, respectively a C₃₋₁₀ cycloalkyl, aryl, arylalkyl orheterocyclic ring radical (each of them such as defined herein), areattached to an oxygen atom or a sulfur atom through a single bond, suchas but not limited to methoxy, ethoxy, propoxy, butoxy, thioethyl,thiomethyl, phenyloxy, benzyloxy, mercaptobenzyl and the like.

As used herein and unless otherwise stated, the term halogen means anyatom selected from the group consisting of fluorine, chlorine, bromineand iodine.

Any substituent designation that is found in more than one site in acompound of this invention shall be independently selected.

As used herein and unless otherwise stated, the term “amino-acid” refersto a radical derived from a molecule having the chemical formulaH₂N—CHR²⁸—COOH, wherein R²⁸ is the side group of atoms characterizingthe amino-acid type; said molecule may be one of the 20naturally-occurring amino-acids or any non naturally-occurringamino-acid. Esters of amino acids included within this definition aresubstituted at one or more carboxyl groups with C₁₋₆ alkyl. This is thecase even when the amino acid is bonded through carboxyl because someamino acids contain more than one carboxyl groups, and in this case theunbonded carboxyl optionally is esterified.

R²⁸ is C₁-C₆ alkyl or C1-C6 alkyl substituted with amino, carboxyl,amide, carboxyl (as well as esters, as noted above), hydroxyl, C₆-C₇aryl, guanidinyl, imidazolyl, indolyl, sulfhydryl, sulfoxide, and/oralkylphosphate. R²⁸ also is taken together with the amino acid αnitrogento form a proline residue (R²⁷ is —(CH₂)₃—). However, R²⁸ is generallythe side group of a naturally-occurring amino acid such as H, —CH₃,—CH(CH₃)₂, —CH₂—CH(CH₃)₂, —CHCHH₃—CH₂—CH₃, —CH₂—C₆H₅, —CH₂CH₂—S—CH₃,—CH₂OH, —CH(OH)—CH₃, —CH₂—SH, —CH₂—C₆H₄OH, —CH₂—CO—NH₂, —CH₂—CH₂—CO—NH₂,—CH₂—COOH, —CH₂—CH₂—COOH, —(CH₂)₄—NH₂ and —(CH₂)₃—NH—C(NH₂)—NH₂. R²⁸also includes 1-guanidinoprop-3-yl, benzyl, 4-hydroxybenzyl,imidazol-4-yl, indol-3-yl, methoxyphenyl and ethoxyphenyl.

Optionally the amino acid residue is a hydrophobic residue such asmono-or di-alkyl or aryl amino acids, cycloalkylamino acids and thelike. Optionally, the residue does not contain a sulfhydryl or guanidinosubstituent.

Naturally-occurring amino acid residues are those residues foundnaturally in plants, animals or microbes, especially proteins thereof.Polypeptides most typically will be substantially composed of suchnaturally-occurring amino acid residues. These amino acids are glycine,alanine, valine, leucine, isoleucine, serine, threonine, cysteine,methionine, glutamic acid, aspartic acid, lysine, hydroxylysine,arginine, histidine, phenylalanine, tyrosine, tryptophan, proline,asparagine, glutamine and hydroxyproline. Additionally, unnatural aminoacids, for example, valanine, phenylglycine and homoarginine are alsoincluded.

Generally, only one of any site in the parental molecule is substitutedwith an amino acid, although it is within the scope of this invention tointroduce amino acids at more than one permitted site. In general, theα-amino or α-carboxyl group of the amino acid are bonded to theremainder of the molecule, i.e., carboxyl or amino groups in the aminoacid side chains generally are not used to form the amide bonds with theparental compound (although these groups may need to be protected duringsynthesis of the conjugates).

The amino acid esters optionally are hydrolyzable in vivo or in vitrounder acidic (pH<3) or basic (pH>10) conditions. Optionally, they aresubstantially stable in the gastrointestinal tract of humans but arehydrolyzed enzymatically in blood or in intracellular environments.

Substituents optionally are designated with or without bonds. Regardlessof bond indications, if a substituent is polyvalent (based on itsposition in the structure referred to), then any and all possibleorientations of the substituent are intended.

Formula's (Z) and (A) depict optional single or double bonds. It will beunderstood that the bonds are present such that the aromatic nature ofthe nucleus of formula (Z) or (A) is preserved, i.e., these formulas areintended to embrace all possible tautomers. For example R²⁵ or R²⁶ willbe absent if the ring N to which they are bonded as indicated in theformula is linked to a flanking ring carbon atom by a double bond. Onthe other hand, R²⁵ or R²⁶ may be present when the N atom to which it isbonded as indicated in the formula is linked to its flanking carbonatoms by single bonds only; in this case aromaticity is accomodated byother substituents, e.g. where R² or R⁴ is oxo.

The compounds of the invention optionally are bound covalently to aninsoluble matrix and used for affinity chromatography (separations,depending on the nature of the groups of the compounds, for examplecompounds with pendant aryl are useful in hydrophobic affinityseparations.

The compounds of the invention are employed for the treatment orprophylaxis of viral infections, more particularly flaviviral orpicornaviral infections, in particular, HCV and BVDV. When using one ormore derivatives of the formula (Z) as defined herein:

-   -   the active ingredients of the compound(s) may be administered to        the mammal (including a human) to be treated by any means well        known in the art, i.e. orally, intranasally, subcutaneously,        intramuscularly, intradermally, intravenously, intra-arterially,        parenterally or by catheterization.    -   the therapeutically effective amount of the preparation of the        compound(s), especially for the treatment of viral infections in        humans and other mammals, preferably is a flaviviral or        picornaviral enzyme inhibiting amount. More preferably, it is a        flaviviral or picornaviral replication inhibiting amount or a        flaviviral or picornaviral enzyme inhibiting amount of the        derivative(s) of formula (Z) as defined herein corresponds to an        amount which ensures a plasma level of between 1 μg/ml and 100        mg/ml, optionally of 10 mg/ml.

This can be achieved by administration of a dosage of in the range of0.001 mg to 20 mg, preferably 0.01 mg to 5 mg, preferably 0.1 mg to 1 mgper day per kg bodyweight for humans. Depending upon the pathologiccondition to be treated and the patient's condition, the said effectiveamount may be divided into several sub-units per day or may beadministered at more than one day intervals.

The present invention further relates to a method for preventing ortreating a viral infections in a subject or patient by administering tothe patient in need thereof a therapeutically effective amountimidazo[4,5-c]pyridine derivatives of the present invention. Thetherapeutically effective amount of the preparation of the compound(s),especially for the treatment of viral infections in humans and othermammals, preferably is a flaviviral or picornaviral enzyme inhibitingamount. More preferably, it is a flaviviral or picornaviral replicationinhibiting amount or a flaviviral or picornaviral enzyme inhibitingamount of the derivative(s) of formula (Z) as defined herein. Suitabledosage is usually in the range of 0.001 mg to 60 mg, optionally 0.01 mgto 10 mg, optionally 0.1 mg to 1 mg per day per kg bodyweight forhumans. Depending upon the pathologic condition to be treated and thepatient's condition, the said effective amount may be divided intoseveral sub-units per day or may be administered at more than one dayintervals.

As is conventional in the art, the evaluation of a synergistic effect ina drug combination may be made by analyzing the quantification of theinteractions between individual drugs, using the median effect principledescribed by Chou et al. in Adv. Enzyme Reg. (1984) 22:27. Briefly, thisprinciple states that interactions (synergism, additivity, antagonism)between two drugs can be quantified using the combination index(hereinafter referred as CI) defined by the following equation:${CI}_{x} = {\frac{{ED}_{x}^{1c}}{{ED}_{x}^{1a}} + \frac{{ED}_{x}^{2c}}{{ED}_{x}^{2a}}}$wherein ED_(x) is the dose of the first or respectively second drug usedalone (1a, 2a), or in combination with the second or respectively firstdrug (1c, 2c), which is needed to produce a given effect. The said firstand second drug have synergistic or additive or antagonistic effectsdepending upon CI<1, CI=1, or CI>1, respectively.

Synergistic activity of the pharmaceutical compositions or combinedpreparations of this invention against viral infection may also bereadily determined by means of one or more tests such as, but notlimited to, the isobologram method, as previously described by Elion etal. in J. Biol. Chem. (1954) 208:477-488 and by Baba et al. inAntimicrob. Agents Chemother. (1984) 25:515-517, using EC₅₀ forcalculating the fractional inhibitory concentration (hereinafterreferred as FIC). When the minimum FIC index corresponding to the FIC ofcombined compounds (e.g., FIC_(x)+FIC_(y)) is equal to 1.0, thecombination is said to be additive; when it is between 1.0 and 0.5, thecombination is defined as subsynergistic, and when it is lower than 0.5,the combination is by defined as synergistic. When the minimum FIC indexis between 1.0 and 2.0, the combination is defined as subantagonisticand, when it is higher than 2.0, the combination is defined asantagonistic.

This principle may be applied to a combination of different antiviraldrugs of the invention or to a combination of the antiviral drugs of theinvention with other drugs that exhibit anti-BVDV or anti-HCV activity.

The invention thus relates to a pharmaceutical composition or combinedpreparation having synergistic effects against a viral infection andcontaining:

-   -   Either:    -   A)    -   (a) a combination of two or more of the imidazo[4,5-c]pyridine        derivatives of the present invention, and    -   (b) optionally one or more pharmaceutical excipients or        pharmaceutically acceptable carriers, for simultaneous, separate        or sequential use in the treatment or prevention of a viral        infection or    -   B)    -   (c) one or more anti-viral agents, and    -   (d) at least one of the imidazo[4,5-c]pyridine derivatives of        the present invention, and    -   (e) optionally one or more pharmaceutical excipients or        pharmaceutically acceptable carriers, for simultaneous, separate        or sequential use in the treatment or prevention of a viral        infection.

Suitable anti-viral agents for inclusion into the synergistic antiviralcompositions or combined preparations of this invention include, forinstance, interferon-alfa (either pegylated or not), ribavirin and otherselective inhibitors of the replication of BVDV or HCV.

The pharmaceutical composition or combined preparation with synergisticactivity against viral infection according to this invention may containthe imidazo[4,5-c]pyridine derivatives of the present invention over abroad content range depending on the contemplated use and the expectedeffect of the preparation. Generally, the content of theimidazo[4,5-c]pyridine derivatives of the present invention of thecombined preparation is within the range of 0.1 to 99.9% by weight,preferably from 1 to 99% by weight, more preferably from 5 to 95% byweight.

According to a particular embodiment of the invention, the compounds ofthe invention may be employed in combination with other therapeuticagents for the treatment or prophylaxis of flaviviral or picornaviralinfections, optionally, HCV and BVDV. The invention therefore relates tothe use of a composition comprising:

-   -   (a) one or more compounds of formula (Z), and    -   (b) one or more Flaviviral or Picornaviral enzyme inhibitors as        biologically active agents in respective proportions such as to        provide a synergistic effect against a viral infection,        particularly a Flaviviral or Picornaviral infection in a mammal,        for instance in the form of a combined preparation for        simultaneous, separate or sequential use in viral infection        therapy, such as of HCV, BVDV and Coxsackie virus. Examples of        such further therapeutic agents for use in combinations include        agents that are effective for the treatment or prophylaxis of        these infections, including interferon alpha, ribavirin, a        compound falling within the scope of disclosure EP1162196, WO        03/010141, WO 03/007945 and WO 03/010140, a compound falling        within the scope of disclosure WO 00/204425, and other patents        or patent applications within their patent families or all the        foregoing filings and/or an inhibitor of flaviviral protease        and/or one or more additional flavivirus polymerase inhibitors.

When using a combined preparation of (a) and (b):

-   -   the active ingredients (a) and (b) may be administered to the        mammal (including a human) to be treated by any means well known        in the art, i.e. orally, intranasally, subcutaneously,        intramuscularly, intradermally, intravenously, intra-arterially,        parenterally or by catheterization.    -   the therapeutically effective amount of the combined preparation        of (a) and (b), especially for the treatment of viral infections        in humans and other mammals, particularly is a flaviviral or        picornaviral enzyme inhibiting amount. More particularly, it is        a fiaviviral or picornaviral replication inhibiting amount of        derivative (a) and a flaviviral or picornaviral enzyme        inhibiting amount of inhibitor (b). Still more particularly when        the said flaviviral or picornaviral enzyme inhibitor (b) is a        polymerase inhibitor, its effective amount is a polymerase        inhibiting amount When the said flaviviral or picornaviral        enzyme inhibitor (b) is a protease inhibitor, its effective        amount is a protease inhibiting amount    -   ingredients (a) and (b) may be administered simultaneously but        it is also beneficial to administer them separately or        sequentially, for instance within a relatively short period of        time (e.g. within about 24 hours) in order to achieve their        functional fusion in the body to be treated.

The invention also relates to the compounds of formula (Z) being usedfor inhibition of the proliferation of other viruses than BVDV, HCV orCoxsackie virus, particularly for the inhibition of other flavivirusesor picornaviruses, with in particular yellow fever virus, Dengue virus,hepatitis B virus, hepatitis G virus, Classical Swine Fever virus or theBorder Disease Virus, and also for the inhibition of HIV and otherretroviruses or lentiviruses.

The present invention further provides veterinary compositionscomprising at least one active ingredient as above defined together witha veterinary carrier therefore, for example in the treatment of BVDV.Veterinary carriers are materials useful for the purpose ofadministering the composition and may be solid, liquid or gaseousmaterials which are otherwise inert or acceptable in the veterinary artand are compatible with the active ingredient. These veterinarycompositions may be administered orally, parenterally or by any otherdesired route.

More generally, the invention relates to the compounds of formula (Z)being useful as agents having biological activity (particularlyantiviral activity) or as diagnostic agents. Any of the uses mentionedwith respect to the present invention may be restricted to a non-medicaluse, a non-therapeutic use, a non-diagnostic use, or exclusively an invitro use, or a use related to cells remote from an animal.

Those of skill in the art will also recognize that the compounds of theinvention may exist in many different protonation states, depending on,among other things, the pH of their environment. While the structuralformulae provided herein depict the compounds in only one of severalpossible protonation states, it will be understood that these structuresare illustrative only, and that the invention is not limited to anyparticular protonation state—any and all protonated forms of thecompounds are intended to fall within the scope of the invention.

The term “pharmaceutically acceptable salts” as used herein means thetherapeutically active non-toxic salt forms which the compounds offormula (Z) are able to form. Therefore, the compounds of this inventionoptionally comprise salts of the compounds herein, especiallypharmaceutically acceptable non-toxic salts containing for example, Na+,Li+, K+, Ca+2 and Mg+2. Such salts may include those derived bycombination of appropriate cations such as alkali and alkaline earthmetal ions or ammonium and quaternary amino ions with an acid anionmoiety, typically a carboxylic acid. The compounds of the invention maybear multiple positive or negative charges. The net charge of thecompounds of the invention may be either positive or negative. Anyassociated counter ions are typically dictated by the synthesis and/orisolation methods by which the compounds are obtained. Typical counterions include, but are not limited to ammonium, sodium, potassium,lithium, halides, acetate, trifluoroacetate, etc., and mixtures thereof.It will be understood that the identity of any associated counter ion isnot a critical feature of the invention, and that the inventionencompasses the compounds in association with any type of counter ion.Moreover, as the compounds can exist in a variety of different forms,the invention is intended to encompass not only forms of the compoundsthat are in association with counter ions (e.g., dry salts), but alsoforms that are not in association with counter ions (e.g., aqueous ororganic solutions). Metal salts typically are prepared by reacting themetal hydroxide with a compound of this invention. Examples of metalsalts which are prepared in this way are salts containing Li+, Na+, andK+. A less soluble metal salt can be precipitated from the solution of amore soluble salt by addition of the suitable metal compound. Inaddition, salts may be formed from acid addition of certain organic andinorganic acids to basic centers, typically amines, or to acidic groups.Examples of such appropriate acids include, for instance, inorganicacids such as hydrohalic acids, e.g. hydrochloric or hydrobromic acid,sulfuric acid, nitric acid, phosphoric acid and the like; or organicacids such as, for example, acetic, propanoic, hydroxyacetic,2-hydroxypropanoic, 2-oxopropanoic, lactic, pyruvic, oxalic (i.e.ethanedioic), malonic, succinic (i.e. butanedioic acid), maleic,fumaric, malic, tartaric, citric, methanesulfonic, ethanesulfonic,benzenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, salicylic (i.e.2-hydroxybenzoic), p-aminosalicylic and the like. Furthermore, this termalso includes the solvates which the compounds of formula (Z) as well astheir salts are able to form, such as for example hydrates, alcoholatesand the like. Finally, it is to be understood that the compositionsherein comprise compounds of the invention in their unionized, as wellas zwitterionic form, and combinations with stoichiometric amounts ofwater as in hydrates.

Also included within the scope of this invention are the salts of theparental compounds with one or more amino acids, especially thenaturally-occurring amino acids found as protein components. The aminoacid typically is one bearing a side chain with a basic or acidic group,e.g., lysine, arginine or glutamic acid, or a neutral group such asglycine, serine, threonine, alanine, isoleucine, or leucine.

The compounds of the invention also include physiologically acceptablesalts thereof. Examples of physiologically acceptable salts of thecompounds of the invention include salts derived from an appropriatebase, such as an alkali metal (for example, sodium), an alkaline earth(for example, magnesium), ammonium and. NX4+ (wherein X is C1-C4 alkyl).Physiologically acceptable salts of an hydrogen atom or an amino groupinclude salts of organic carboxylic acids such as acetic, benzoic,lactic, fumaric, tartaric, maleic, malonic, malic, isethionic,lactobionic and succinic acids; organic sulfonic acids, such asmethanesulfonic, ethanesulfonic, benzenesulfonic and p-toluenesulfonicacids; and inorganic acids, such as hydrochloric, sulfuric, phosphoricand sulfamic acids. Physiologically acceptable salts of a compoundcontaining a hydroxy group include the anion of said compound incombination with a suitable cation such as Na+ and NX4+ (wherein Xtypically is independently selected from H or a C1-C4 alkyl group).However, salts of acids or bases which are not physiologicallyacceptable may also find use, for example, in the preparation orpurification of a physiologically acceptable compound. All salts,whether or not derived form a physiologically acceptable acid or base,are within the scope of the present invention.

As used herein and unless otherwise stated, the term “enantiomer” meanseach individual optically active form of a compound of the invention,having an optical purity or enantiomeric excess (as determined bymethods standard in the art) of at least 80% (i.e. at least 90% of oneenantiomer and at most 10% of the other enantiomer), preferably at least90% and more preferably at least 98%.

The term “isomers” as used herein means all possible isomeric forms,including tautomeric and sterochemical forms, which the compounds offormula (Z) may possess, but not including position isomers. Typically,the structures shown herein exemplify only one tautomeric or resonanceform of the compounds, but the corresponding alternative configurationsare contemplated as well. Unless otherwise stated, the chemicaldesignation of compounds denotes the mixture of all possiblestereochemically isomeric forms, said mixtures containing alldiastereomers and enantiomers (since the compounds of formula (Z) mayhave at least one chiral center) of the basic molecular structure, aswell as the stereochemically pure or enriched compounds. Moreparticularly, stereogenic centers may have either the R— orS-configuration, and multiple bonds may have either cis- ortrans-configuration.

Pure isomeric forms of the said compounds are defined as isomerssubstantially free of other enantiomeric or diastereomeric forms of thesame basic molecular structure. In particular, the term“stereoisomerically pure” or “chirally pure” relates to compounds havinga stereoisomeric excess of at least about 80% (i.e. at least 90% of oneisomer and at most 10% of the other possible isomers), preferably atleast 90%, more preferably at least 94% and most preferably at least97%. The terms “enantionierically pure” and “diastereomerically pure”should be understood in a similar way, having regard to the enantiomericexcess, respectively the diastereomeric excess, of the mixture inquestion.

Separation of stereoisomers is accomplished by standard methods known tothose in the art. One enantiomer of a compound of the invention can beseparated substantially free of its opposing enantiomer by a method suchas formation of diastereomers using optically active resolving agents(“Stereochemistry of Carbon Compounds,” (1962) by E. L. Eliel, McGrawHill; Lochmuller, C. H., (1975) J. Chromatogr., 113:(3) 283-302).Separation of isomers in a mixture can be accomplished by any suitablemethod, including: (1) formation of ionic, diastereomeric salts withchiral compounds and separation by fractional crystallization or othermethods, (2) formation of diastereomeric compounds with chiralderivatizing reagents, separation of the diastereomers, and conversionto the pure enantiomers, or (3) enantiomers can be separated directlyunder chiral conditions. Under method (1), diastereomeric salts can beformed by reaction of enantiomerically pure chiral bases such asbromine, quinine, ephedrine, strychnine, a-methyl-b-phenylethylamine(amphetamine), and the like with asymmetric compounds bearing acidicfunctionality, such as carboxylic acid and sulfonic acid. Thediastereomeric salts may be induced to separate by fractionalcrystallization or ionic chromatography. For separation of the opticalisomers of amino compounds, addition of chiral carboxylic or sulfonicacids, such as camphorsulfonic acid, tartaric acid, mandelic acid, orlactic acid can result in formation of the diastereomeric salts.Alternatively, by method (2), the substrate to be resolved may bereacted with one enantiomer of a chiral compound to form adiastereomeric pair (Eliel, E. and Wilen, S. (1994) Stereochemistry ofOrganic Compounds, John Wiley & Sons, Inc., p. 322). Diastereomericcompounds can be formed by reacting asymmetric compounds withenantiomerically pure chiral derivatizing reagents, such as methylderivatives, followed by separation of the diastereomers and hydrolysisto yield the free, enantiomerically enriched xanthene. A method ofdetermining optical purity involves making chiral esters, such as amenthyl ester or Mosher ester, a-methoxy-a-(trifuoromethyl)phenylacetate (Jacob III. (1982) J. Org. Chem. 47:4165), of the racemicmixture, and analyzing the NMR spectrum for the presence of the twoatropisomeric diastereomers. Stable diastereomers can be separated andisolated by normal- and reverse-phase chromatography following methodsfor separation of atropisomeric naphthyl-isoquinolines (Hoye, T., WO96/15111). Under method (3), a racemic mixture of two asymmetricenantiomers is separated by chromatography using a chiral stationaryphase. Suitable chiral stationary phases are, for example,polysaccharides, in particular cellulose or amylose derivatives.Commercially available polysaccharide based chiral stationary phases areChiralCeI™ CA, OA, OB5, OC5, OD, OF, OG, OJ and OK, and ChiralpakTM AD,AS, OP(+) and OT(+). Appropriate eluents or mobile phases for use incombination with said polysaccharide chiral stationary phases are hexaneand the like, modified with an alcohol such as ethanol, isopropanol andthe like. (“Chiral Liquid Chromatography” (1989) W. J. Lough, Ed.Chapman and Hall, New York; Okamoto, (1990) “Optical resolution ofdihydropyridine enantiomers by High-performance liquid chromatographyusing phenylcarbamates of polysaccharides as a chiral stationary phase”,J. of Chromatogr. 513:375-378).

The terms cis and trans are used herein in accordance with ChemicalAbstracts nomenclature and include reference to the position of thesubstituents on a ring moiety. The absolute stereochemical configurationof the compounds of formula (1) may easily be determined by thoseskilled in the art while using well-known methods such as, for example,X-ray diffraction.

The compounds of the invention may be formulated with conventionalcarriers and excipients, which will be selected in accord with ordinarypractice. Tablets will contain excipients, glidants, fillers, bindersand the like. Aqueous formulations are prepared in sterile form, andwhen intended for delivery by other than oral administration generallywill be isotonic. Formulations optionally contain excipients such asthose set forth in the “Handbook of Pharmaceutical Excipients” (1986)and include ascorbic acid and other antioxidants, chelating agents suchas EDTA, carbohydrates such as dextrin, hydroxyalkylcellulose,hydroxyalkylmethylcellulose, stearic acid and the like.

Subsequently, the term “pharmaceutically acceptable carrier” as usedherein means any material or substance with which the active ingredientis formulated in order to facilitate its application or dissemination tothe locus to be treated, for instance by dissolving, dispersing ordiffusing the said composition, and/or to facilitate its storage,transport or handling without impairing its effectiveness. Thepharmaceutically acceptable carrier may be a solid or a liquid or a gaswhich has been compressed to form a liquid, i.e. the compositions ofthis invention can suitably be used as concentrates, emulsions,solutions, granulates, dusts, sprays, aerosols, suspensions, ointments,creams, tablets, pellets or powders.

Suitable pharmaceutical carriers for use in the said pharmaceuticalcompositions and their formulation are well known to those skilled inthe art, and there is no particular restriction to their selectionwithin the present invention. They may also include additives such aswetting agents, dispersing agents, stickers, adhesives, emulsifyingagents, solvents, coatings, antibacterial and antifungal agents (forexample phenol, sorbic acid, chlorobutanol), isotonic agents (such assugars or sodium chloride) and the like, provided the same areconsistent with pharmaceutical practice, i.e. carriers and additiveswhich do not create permanent damage to mammals. The pharmaceuticalcompositions of the present invention may be prepared in any knownmanner, for instance by homogeneously mixing, coating and/or grindingthe active ingredients, in a one-step or multi-steps procedure, with theselected carrier material and, where appropriate, the other additivessuch as surface-active agents may also be prepared by inicronisation,for instance in view to obtain them in the form of microspheres usuallyhaving a diameter of about 1 to 10 gm, namely for the manufacture ofmicrocapsules for controlled or sustained release of the activeingredients.

Suitable surface-active agents, also known as emulgent or emulsifier, tobe used in the pharmaceutical compositions of the present invention arenon-ionic, cationic and/or anionic materials having good emulsifying,dispersing and/or wetting properties. Suitable anionic surfactantsinclude both water-soluble soaps and water-soluble syntheticsurface-active agents. Suitable soaps are alkaline or alkaline-earthmetal salts, unsubstituted or substituted ammonium salts of higher fattyacids (C₁₀-C₂₂), e.g. the sodium or potassium salts of oleic or stearicacid, or of natural fatty acid mixtures obtainable form coconut oil ortallow oil. Synthetic surfactants include sodium or calcium salts ofpolyacrylic acids; fatty sulphonates and sulphates; sulphonatedbenzimidazole derivatives and alkylarylsulphonates. Fatty sulphonates orsulphates are usually in the form of alkaline or alkaline-earth metalsalts, unsubstituted ammonium salts or ammonium salts substituted withan alkyl or acyl radical having from 8 to 22 carbon atoms, e.g. thesodium or calcium salt of lignosulphonic acid or dodecylsulphonic acidor a mixture of fatty alcohol sulphates obtained from natural fattyacids, alkaline or alkaline-earth metal salts of sulphuric or sulphonicacid esters (such as sodium lauryl sulphate) and sulphonic acids offatty alcohol/ethylene oxide adducts. Suitable sulphonated benzimidazolederivatives preferably contain 8 to 22 carbon atoms. Examples ofalkylarylsulphonates are the sodium, calcium or alcanolamine salts ofdodecylbenzene sulphonic acid or dibutyl-naphtalenesulphonic acid or anaphtalene-sulphonic acid/formaldehyde condensation product. Alsosuitable are the corresponding phosphates, e.g. salts of phosphoric acidester and an adduct of p-nonylphenol with ethylene and/or propyleneoxide, or phospholipids. Suitable phospholipids for this purpose are thenatural (originating from animal or plant cells) or syntheticphospholipids of the cephalin or lecithin type such as e.g.phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerine,lysolecithin, cardiolipin, dioctanylphosphatidyl-choline,dipalritoylphoshatidyl-choline and their mixtures.

Suitable non-ionic surfactants include polyethoxylated andpolypropoxylated derivatives of alkylphenols, fatty alcohols, fattyacids, aliphatic amines or amides containing at least 12 carbon atoms inthe molecule, alkylarenesulphonates and dialkylsulphosuccinates, such aspolyglycol ether derivatives of aliphatic and cycloaliphatic alcohols,saturated and unsaturated fatty acids and alkylphenols, said derivativespreferably containing 3 to 10 glycol ether groups and 8 to 20 carbonatoms in the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atoms inthe alkyl moiety of the alkylphenol. Further suitable non-ionicsurfactants are water-soluble adducts of polyethylene oxide withpoylypropylene glycol, ethylenediaminopolypropylene glycol containing 1to 10 carbon atoms in the alkyl chain, which adducts contain 20 to 250ethyleneglycol ether groups and/or 10 to 100 propyleneglycol ethergroups. Such compounds usually contain from 1 to 5 ethyleneglycol unitsper propyleneglycol unit. Representative examples of non-ionicsurfactants are nonylphenol-polyethoxyethanol, castor oil polyglycolicethers, polypropylene/polyethylene oxide adducts,tributylphenoxypolyethoxyethanol, polyethyleneglycol andoctylphenoxypolyethoxyethanol. Fatty acid esters of polyethylenesorbitan (such as polyoxyethylene sorbitan trioleate), glycerol,sorbitan, sucrose and pentaerythritol are also suitable non-ionicsurfactants.

Suitable cationic surfactants include quaternary ammonium salts,particularly halides, having 4 hydrocarbon radicals optionallysubstituted with halo, phenyl, substituted phenyl or hydroxy; forinstance quaternary ammonium salts containing as N-substituent at leastone C8C22 alkyl radical (e.g. cetyl, lauryl, palmityl, myristyl, oleyland the like) and, as further substituents, unsubstituted or halogenatedlower alkyl, benzyl and/or hydroxy-lower alkyl radicals.

A more detailed description of surface-active agents suitable for thispurpose may be found for instance in “McCutcheon's Detergents andEmulsifiers Annual” (MC Publishing Crop., Ridgewood, N.J., 1981),“Tensid-Taschenbucw”, 2 d ed. (Hanser Verlag, Vienna, 1981) and“Encyclopaedia of Surfactants, (Chemical Publishing Co., New York,1981).

Compounds of the invention and their physiologically acceptable salts(hereafter collectively referred to as the active ingredients) may beadministered by any route appropriate to the condition to be treated,suitable routes including oral, rectal, nasal, topical (includingocular, buccal and sublingual), vaginal and parenteral (includingsubcutaneous, intramuscular, intravenous, intradermal, intrathecal andepidural). The preferred route of administration may vary with forexample the condition of the recipient.

While it is possible for the active ingredients to be administered aloneit is preferable to present them as pharmaceutical formulations. Theformulations, both for veterinary and for human use, of the presentinvention comprise at least one active ingredient, as above described,together with one or more pharmaceutically acceptable carriers thereforeand optionally other therapeutic ingredients. The carrier(s) optimallyare “acceptable” in the sense of being compatible with the otheringredients of the formulation and not deleterious to the recipientthereof. The formulations include those suitable for oral, rectal,nasal, topical (including buccal and sublingual), vaginal or parenteral(including subcutaneous, intramuscular, intravenous, intradermal,intrathecal and epidural) administration. The formulations mayconveniently be presented in unit dosage form and may be prepared by anyof the methods well known in the art of pharmacy. Such methods includethe step of bringing into association the active ingredient with thecarrier which constitutes one or more accessory ingredients. In generalthe formulations are prepared by uniformly and intimately bringing intoassociation the active ingredient with liquid carriers or finely dividedsolid carriers or both, and then, if necessary, shaping the product.

Formulations of the present invention suitable for oral administrationmay be presented as discrete units such as capsules, cachets or tabletseach containing a predetermined amount of the active ingredient; as apowder or granules; as solution or a suspension in an aqueous liquid ora non-aqueous liquid; or as an oil-in-water liquid emulsion or awater-in-oil liquid emulsion. The active ingredient may also bepresented as a bolus, electuary or paste.

A tablet may be made by compression or molding, optionally with one ormore accessory ingredients. Compressed tablets may be prepared bycompressing in a suitable machine the active ingredient in afree-flowing form such as a powder or granules, optionally mixed with abinder, lubricant, inert diluent, preservative, surface active ordispersing agent. Molded tablets may be made by molding in a suitablemachine a mixture of the powdered compound moistened with an inertliquid diluent. The tablets may optionally be coated or scored and maybe formulated so as to provide slow or controlled release of the activeingredient therein. For infections of the eye or other external tissuese.g. mouth and skin, the formulations are optionally applied as atopical ointment or cream containing the active ingredient(s) in anamount of, for example, 0.075 to 20% w/w (including active ingredient(s)in a range between 0.1% and 20% in increments of 0.1% w/w such as 0.6%w/w, 0.7% w/w, etc), preferably 0.2 to 15% w/w and most preferably 0.5to 10% w/w. When formulated in an ointment, the active ingredients maybe employed with either a paraffinic or a water-miscible ointment base.Alternatively, the active ingredients may be formulated in a cream withan oil-in-water cream base. If desired, the aqueous phase of the creambase may include, for example, at least 30% w/w of a polyhydric alcohol,i.e. an alcohol having two or more hydroxyl groups such as propyleneglycol, butane 1,3-diol, mannitol, sorbitol, glycerol and polyethyleneglycol (including PEG400) and mixtures thereof. The topical formulationsmay desirably include a compound which enhances absorption orpenetration of the active ingredient through the skin or other affectedareas. Examples of such dermal penetration enhancers includedimethylsulfoxide and related analogs.

The oily phase of the emulsions of this invention may be constitutedfrom known ingredients in a known manner. While the phase may comprisemerely an emulsifier (otherwise known as an emulgent), it desirablycomprises a mixture of at least one emulsifier with a fat or an oil orwith both a fat and an oil. Optionally, a hydrophilic emulsifier isincluded together with a lipophilic emulsifier which acts as astabilizer. It is also preferred to include both an oil and a fat.Together, the emulsifier(s) with or without stabilizer(s) make up theso-called emulsifying wax, and the wax together with the oil and fatmake up the so-called emulsifying ointment base which forms the oilydispersed phase of the cream formulations.

The choice of suitable oils or fats for the formulation is based onachieving the desired cosmetic properties, since the solubility of theactive compound in most oils likely to be used in pharmaceuticalemulsion formulations is very low. Thus the cream should optionally be anon-greasy, non-staining and washable product with suitable consistencyto avoid leakage from tubes or other containers. Straight or branchedchain, mono- or dibasic alkyl esters such as di-isoadipate, isocetylstearate, propylene glycol diester of coconut fatty acids, isopropylmyristate, decyl oleate, isopropyl palmitate, butyl stearate,2-ethylhexyl palmitate or a blend of branched chain esters known asCrodamol CAP may be used, the last three being preferred esters. Thesemay be used alone or in combination depending on the propertiesrequired. Alternatively, high melting point lipids such as white softparaffin and/or liquid paraffin or other mineral oils can be used.

Formulations suitable for topical administration to the eye also includeeye drops wherein the active ingredient is dissolved or suspended in asuitable carrier, especially an aqueous solvent for the activeingredient. The active ingredient is optionally present in suchformulations in a concentration of 0.5 to 20%, advantageously 0.5 to 10%particularly about 1.5% w/w. Formulations suitable for topicaladministration in the mouth include lozenges comprising the activeingredient in a flavored basis, usually sucrose and acacia ortragacanth; pastilles comprising the active ingredient in an inert basissuch as gelatin and glycerin, or sucrose and acacia; and mouthwashescomprising the active ingredient in a suitable liquid carrier.

Formulations for rectal administration may be presented as a suppositorywith a suitable base comprising for example cocoa butter or asalicylate. Formulations suitable for nasal administration wherein thecarrier is a solid include a coarse powder having a particle size forexample in the range 20 to 500 microns (including particle sizes in arange between 20 and 500 microns in increments of 5 microns such as 30microns, 35 microns, etc), which is administered in the manner in whichsnuff is taken, i.e. by rapid inhalation through the nasal passage froma container of the powder held close up to the nose. Suitableformulations wherein the carrier is a liquid, for administration as forexample a nasal spray or as nasal drops, include aqueous or oilysolutions of the active ingredient. Formulations suitable for aerosoladministration may be prepared according to conventional methods and maybe delivered with other therapeutic agents.

Formulations suitable for vaginal administration may be presented aspessaries, tampons, creams, gels, pastes, foams or spray formulationscontaining in addition to the active ingredient such carriers as areknown in the art to be appropriate.

Formulations suitable for parenteral administration include aqueous andnon-aqueous sterile injection solutions which may contain anti-oxidants,buffers, bacteriostats and solutes which render the formulation isotonicwith the blood of the intended recipient; and aqueous and non-aqueoussterile suspensions which may include suspending agents and thickeningagents. The formulations may be presented in unit-dose or multi-dosecontainers, for example sealed ampoules and vials, and may be stored ina freeze-dried (lyophilized) condition requiring only the addition ofthe sterile liquid carrier, for example water for injections,immediately prior to use. Extemporaneous injection solutions andsuspensions may be prepared from sterile powders, granules and tabletsof the kind previously described.

Preferred unit dosage formulations are those containing a daily dose orunit daily sub-dose, as herein above recited, or an appropriate fractionthereof, of an active ingredient.

It should be understood that in addition to the ingredients particularlymentioned above the formulations of this invention may include otheragents conventional in the art having regard to the type of formulationin question, for example those suitable for oral administration mayinclude flavoring agents.

Compounds of the invention can be used to provide controlled releasepharmaceutical formulations containing as active ingredient one or morecompounds of the invention (“controlled release formulations”) in whichthe release of the active ingredient can be controlled and regulated toallow less frequency dosing or to improve the pharmacokinetic ortoxicity profile of a given invention compound. Controlled releaseformulations adapted for oral administration in which discrete unitscomprising one or more compounds of the invention can be preparedaccording to conventional methods.

Additional ingredients may be included in order to control the durationof action of the active ingredient in the composition. Control releasecompositions may thus be achieved by selecting appropriate polymercarriers such as for example polyesters, polyamino acids, polyvinylpyrrolidone, ethylene-vinyl acetate copolymers, methylcellulose,carboxymethylcellulose, protamine sulfate and the like. The rate of drugrelease and duration of action may also be controlled by incorporatingthe active ingredient into particles, e.g. microcapsules, of a polymericsubstance such as hydrogels, polylactic acid, hydroxymethylcellulose,polymethyl methacrylate and the other above-described polymers. Suchmethods include colloid drug delivery systems like liposomes,microspheres, microemulsions, nanoparticles, nanocapsules and so on.Depending on the route of administration, the pharmaceutical compositionmay require protective coatings. Pharmaceutical forms suitable forinjectionable use include sterile aqueous solutions or dispersions andsterile powders for the extemporaneous preparation thereof. Typicalcarriers for this purpose therefore include biocompatible aqueousbuffers, ethanol, glycerol, propylene glycol, polyethylene glycol andthe like and mixtures thereof.

In view of the fact that, when several active ingredients are used incombination, they do not necessarily bring out their joint therapeuticeffect directly at the same time in the mammal to be treated, thecorresponding composition may also be in the form of a medical kit orpackage containing the two ingredients in separate but adjacentrepositories or compartments. In the latter context, each activeingredient may therefore be formulated in a way suitable for anadministration route different from that of the other ingredient, e.g.one of them may be in the form of an oral or parenteral formulationwhereas the other is in the form of an ampoule for intravenous injectionor an aerosol.

The compounds of formula (Z), (A), (I), (II), (IlI), (IV), (V) and (VI)can be prepared while using a series of chemical reactions well known tothose skilled in the art, altogether making up the process for preparingsaid compounds and exemplified further. The processes described furtherare only meant as examples and by no means are meant to limit the scopeof the present invention.

General Methods and Materials for the Preparation of the Compounds ofthe Invention:

The compounds according to the invention are conveniently prepared intwo steps; known to to the skilled person. First, a (substituted)3,4-diaminopyridine (A) is reacted with B to giveimidazo[4,5-c]pyridines C (scheme 1). If Y is COOH, then the cyclizationis carried out under acidic catalysis (preferably in polyphosphoric acidat a temperature between 90 and 200° C.); other methods include reactionin 4N hydrochloric acid at reflux temperature or neat at a temperaturebetween 90 and 180° C. (for aliphatic carboxylic acids). In the case ofacid-sensitive groups like alkoxy or thiophene, the reaction can becarried out in phosphorus oxychloride at a temperature between 70 and120° C. Alternatively, reaction with aldehydes (Y═CHO) or theirbisulfite adducts under oxidative conditions (nitrobenzene, DDQ,copper(II)acetate, O₂, sulfur etc.) gives imidazo[4,5-c]pyridines C.Other methods are the reaction of (substituted) 3,4-diaminopyridines (A)with orthoesters (Y═C(OR)₃), anhydrides (Y═OCOOR) or acid halogenides(Y═COX), etc.

The imidazo[4,5-c]pyridines C can be formulated in three tautomericforms (1H, 3H or 5H), as shown in scheme 2.

Substituents (R², R⁴ and/or R⁵≠H) can be introduced by two ways: i)either by cyclization of an appropriately substituted3,4-diaminopyridine A or ii) by introduction of the substituent(s) ontothe imidazo[4,5-c]pyridine C. For example, halogens can be introduced inposition 7 of the imidazo[4,5-c]pyridine C by direct halogenation(R⁵═Br: with bromine in acetic acid or with NBS in acetic acid; R⁵═Cl:with chlorine in acetic acid or with NCS in acetic acid). Anotherexample is the direct nitration (R⁵═NO₂), followed by reduction to givethe amino group (R⁵═NH₂). Substituents in position 4 of theimidazo[4,5-c]pyridine C can be introduced, for example, via thecorresponding imidazo[4,5-c]pyridine N⁵-oxides.

Substituted 3,4-diaminopyridines can, for example, be prepared accordingto the following route (scheme 3): Nitration (HNO₃/H₂SO₄) of a 2- or3-substituted pyridine N-oxide gives the corresponding 4-nitro product.Double reduction of the N-oxide and the nitro group with iron in aceticacid gives the 2- or 3-substituted 4-aminopyridine. Subsequent nitration(HNO₃/H₂SO₄) and reduction of the nitro group with iron in a mixture ofconcentrated hydrochloric acid and ethanol gives the desired substituted3,4-diaminopyridines.

In the case of the 3-substituted pyridines as starting materials5-substituted 3,4-diaminopyridines are obtained. Nitration of2-substituted 4-aminopyridines gives mixtures of 3- and5-nitropyridines, with 3-nitration as the predominant reaction.

4-Amino-2-methoxy-3-nitropyridine can be prepared by reaction of4-amino-2-chloro-3-nitropyridine with sodium methoxide. 3-Substituted4-aminopyridines can also be prepared by electrophilic substitution of4-aminopyridines (e.g. chlorination, bromination etc.).4-Amino-3-bromo-5-nitropyridine can be obtained by bromination of4-amino-3-nitropyridine.

The second and final step is the reaction of the imidazo[4,5]pyridines Cwith an alkylating agent D (R⁶═Cl, Br, etc.) in an appropriate solvent(preferably DMF) under addition of a base (preferably aqueous sodiumhydroxide) at ambient temperature (scheme 4).

This reaction gives mixtures of three products (alkylation at the N¹, N³or N⁵ of the imidazo[4,5-c]pyridine C, respectively). For example,reaction of imidazo[4,5-c]pyridine C R¹═2,6-difluorophenyl, R²═R⁴═R⁵═H)with 2,6-difluorobenzyl bromide gave the following mixture (scheme 5):

This mixture can be separated by column chromatography (silica gel,eluent: mixture of dichloromethane and methanol). The structures of theisolated components can then be assigned by NMR spectroscopy (forexample by one-dimensional NOE-techniques: irradiation at the CH₂resonance frequency; applying this to GPRTI-8 gives signal enhancementsof the protons in positions 4 and 6 of the imidazo[4,5-c]pyridineringsystem) or by single crystal x-ray analysis.

Alternatively, the crude reaction mixture can be recrystallized from anappropriate solvent (mixture), e.g. from a mixture of diisopropyl etherand ethyl acetate, to give the pure N⁵ alkylated products.

(Hetero)aromatic substituents on (hetero)aromatic rings (R², R⁴, R⁵, R⁶,R¹⁷, R¹⁹) can be introduced by crosscoupling reactions, e.g. Suzukicoupling.

In the case of hydroxy, mercapto or amino substituents in position 4 or6 of the imidazopyridine I (Z=O, S or NR), tautomers can be formulated:

Therefore, an additional substituent (R²⁵) can be introduced at position1 or 3 of the imidazo[4,5-c]pyridine:

Compounds of general structure E, F, G and H can be prepared byalkylation (for example with (cyclo)alkylbromide or (cyclo)alkyliodideetc.) of the corresponding 1(3)H-imidazo[4,5-c]pyridin 4ones (Z=O) or-thiones (Z=S) or -one-imines (Z=NR), or1(3)H-imidazo[4,5-c]pyridin-6-ones or -thiones or -one-imines,respectively (scheme 6). The resulting mixtures can be separated bycolumn chromatography. The required 1(3)H-imidazo[4,5-c]pyridine-4-onesor -thiones or -one-imines, or 1(3)H-imidazo[4,5-c]pyridine-6-ones or-thiones or -one-imines can, for example, be prepared from thecorresponding 4- or 6-chloro-imidazo[4,5-c]pyridines by nucleophilicsubstitution. 1(3)H-Imidazo[4,5-c]pyridine-4-ones or -6-ones can also beprepared by ether cleavage of the corresponding 4 or6-alkoxy-imidazo[4,5-c]pyridines.

Alternatively, compounds of general structures E and G (Z=O) can besynthesized starting from (substituted) 2,4-dihydroxy-3-nitropyridine(scheme 7) or (substituted) 2,4dihydroxy-5-nitropyridine, respectively.Introduction of the substituent in position 1 of the pyridine (forexample by alkylation), followed by subsequent reaction with POCl₃ andan appropriate amine, reduction of the nitro function and cyclizationgives the desired imidazo[4,5-c]pyridines E or G. These can betransformed into the corresponding thiones by reaction withphosphorus(V)-sulfide or Laweson's reagent or into the correspondingone-imines by reaction with phosphorus(III)-chloride/amine.

Another methods to introduce R²⁵ or R²⁶, respectively, is by reductiveamination with a carbonyl reagent and sodiumcyanoborohydride, asexemplified in scheme 8:

Monobenzoylation of a (substituted) 3,4-diaminopyridine, followed byreductive amination and cyclization gives the 1- or 3-substitutedimidazo[4,5-c]pyridine. Quaternization, for example with a benzylbromide, followed by cleavage of the 4-methoxy function, results in thedesired imidazo[4,5-c]pyridinone.

Introduction of a carboxylic function (carboxylic acid, ester, amide) inposition 6 of the imidazo[4,5-c]pyridine can be achieved by differentroutes. One involves the imidazo[4,5-c]pyridine N⁵-oxide (for exampleobtained by N-oxidation of the corresponding imidazo[4,5-c]pyridine withmeta-chlorperbenzoic acid (MCPBA) or with H₂O₂/methyl-trioxorhenium),which can be brominated in position 6. Removal of the N-oxygen (e.g.with iron in acetic acid), bromine/lithium exchange, for example withn-BuLi, followed by reaction with carbon dioxide, gives the desired6-carboxy compounds. Another method is the conversion of the 6-bromosubstituent into a carboxylic ester function by reaction with carbonmonoxide in alcohol with palladium acetate as the catalyst. Yet anotherpossibility is the reaction of the 4-substituted N⁵-oxide withtrimethylsilylcyanide/N,N-diethylcarbamoylchloride to give the 6-cyanoproduct, which can be hydrolysed to the corresponding 6-carboxylic acid.

The 5-substituted idazo[4,5-c]pyridin-6-ones can be prepared by similarmethodologies, as shown in scheme 10.

The 6-carboxy group can easily be converted into an amide function byreaction with an amine using DCC (dicyclohexyl carbodiimide):

Alternatively, carboxyl groups can be introduced by oxidation (e.g. withKMnO₄) of the corresponding methyl analogues (scheme 12)

Scheme 13 shows further examples for the synthesis of compounds with asubstituted (het)aryl in position 2 of the imidazo[4,5-c]pyridineringsystem.

Analogous compounds are synthesized in the same fashion as in theforegoing schemes by varying the stating materials, intermediates,solvents and conditions as will be known by those skilled in the art.

EXAMPLES

The following examples illustrate the present invention without beinglimited thereto. Part A represent the preparation of the compoundswhereas Part B represents the pharmacological examples. TABLE 8Structures of examples and their respective codes

Entry code X Y R¹ R² R³ R⁴ R⁵ 1 GPRTI-8 CH₂ — 2,6-difluorophenyl H2,6-difluorophenyl H H 2 GPJN-1 CH₂ — 2,6-difluorophenyl H phenyl H H 3GPJN-2 CH₂ — 2,6-difluorophenyl H phenyl H H 4 GPJN-3 CH₂ — phenyl H2,6-difluorophenyl H H 5 GPJN-4 CH₂ — phenyl H phenyl H H 6 GPJN-7 CH₂ —phenyl H 2-chorophenyl H H 7 GPJN-8 CH₂ — phenyl H 3-chorophenyl H H 8GPJN-9 CH₂ — phenyl H 4-chorophenyl H H 9 GPJN-11 CH₂ — phenyl H2-methoxyphenyl H H 10 GPJN-12 CH₂ — phenyl H 3-methoxyphenyl H H 11GPJN-13 CH₂ — phenyl H 4-methoxyphenyl H H 12 GPJN-14 (CH₂)₃ — phenyl Hphenyl H H 13 GPJN-15 CH₂ — phenyl H 4-methylphenyl H H 14 GPJN-16 CH₂ —phenyl H 4-(1,1-dimethylethyl)phenyl H H 15 GPJN-17 CH₂ — phenyl H2-fluorophenyl H H 16 GPJN-18 CH₂ — phenyl H 3-fluorophenyl H H 17GPJN-19 CH₂ — phenyl H 4-fluorophenyl H H 18 GPJN-20 CH₂ — phenyl H2-methylphenyl H H 19 GPJN-21 CH₂ — phenyl H 3-methylphenyl H H 20GPJN-22 CH — phenyl H 4-bromophenyl H H 21 GPJN-23 CH₂ — phenyl H4-cyanophenyl H H 22 GPJN-24 CH₂ — phenyl H 4-(trifluoromethyl)phenyl HH 23 GPJN-25 CH₂ — phenyl H 5-chloro-2-thienyl H H 24 GPJN-26 CH₂ —phenyl H 2-naphthalenyl H H 25 GPJN-27 (CH₂)₄ — phenyl H phenyl H H 26GPJN-31 CH₂ — phenyl H 4-pyridinyl H H 27 GPJN-32 CH₂ — phenyl H4-phenyl-phenyl H H 28 GPJN-33 CH(CH₃) — phenyl H phenyl H H 29 GPJN-34CH₂ — phenyl H 2-pyridinyl H H 30 GPJN-35 CH₂ — phenyl H 3-pyridinyl H H31 GPJN-36 CH₂ — phenyl H 1-naphthalenyl H H 32 GPJN-37 CH₂ — phenyl Hcyclohexyl H H 33 GPJN-39 CH₂ — 2,6-difluorophenyl H 4-fluorophenyl H H34 GPJN-40 CH₂ — 2,6-difluorophenyl H 2,4-difluorophenyl H H 35 GPJN-41CH₂ — 2,6-difluorophenyl H 2,4,6-trifluorophenyl H H 36 GPJN-42 CH₂ —phenyl H 2-bromophenyl H H 37 GPJN-43 CH₂ — phenyl H 3-bromophenyl H H38 GPJN-44 CH₂ — phenyl H 2-cyanophenyl H H 39 GPJN-45 CH₂ — phenyl H3-cyanophenyl H H 40 GPJN-46 CH₂ — phenyl H 2-(trifluoromethyl)phenyl HH 41 GPJN-47 CH₂ — phenyl H 3-(trifluoromethyl)phenyl H H 42 GPJN-48 CH₂(CH₂)₂ H H 4-bromophenyl H H 43 GPJN-49 CH₂ — 4-pyridyl H 4-bromophenylH H 44 GPJN-50 CH₂ — 3-fluorophenyl H 4-bromophenyl H H 45 GPJN-51 CH₂ —4-fluorophenyl H 4-bromophenyl H H 46 GPJN-52 CH₂ — 2-fluorophenyl H4-bromophenyl H H 47 GPJN-53 CH₂ — 2-thienyl H 4-bromophenyl H H 48GPJN-54 CH₂ — 2-chlorophenyl H 4-bromophenyl H H 49 GPJN-55 CH₂ —3-chlorophenyl H 4-bromophenyl H H 50 GPJN-56 CH₂ — 4-chlorophenyl H4-bromophenyl H H 51 GPJN-57 CH₂ — 3-pyridyl H 4-bromophenyl H H 52GPJN-58 CH₂ — 2-pyridyl H 4-bromophenyl H H 53 GPJN-59 CH₂ —2-methylphenyl H 4-bromophenyl H H 54 GPJN-60 CH₂ — 3-methylphenyl H4-bromophenyl H H 55 GPJN-61 CH₂ — 4-methylphenyl H 4-bromophenyl H H 56GPJN-62 CH₂ — 1-naphtalenyl H 4-bromophenyl H H 57 GPJN-63 CH₂ —2-naphtalenyl H 4-bromophenyl H H 58 GPJN-64 CH₂ — 3-methoxyphenyl H4-bromophenyl H H 59 GPJN-65 CH₂ — 3-bromophenyl H 4-bromophenyl H H 60GPJN-66 CH₂ — 3- H 4-bromophenyl H H (dimethylamino)phenyl 61 GPJN-67CH₂ (CH₂)₁ phenyl H 4-bromophenyl H H 62 GPJN-68 CH₂ — phenyl H4-iodophenyl H H 63 GPJN-69 CH₂ — 3-iodophenyl H 4-bromophenyl H H 64GPJN-70 CH₂ — 2-bromophenyl H 4-bromophenyl H H 65 GPJN-73 O—CH₂—CH₂ -phenyl H phenyl H H 66 GPJN-74 CH₂ — phenyl H 3,4-dichlorophenyl H H 67GPJN-75 CH═CH— — phenyl H phenyl H H CH₂ 68 GPJN-76 CH₂ (CH₂)₂ phenyl H4-bromophenyl H H 69 GPJN-77 CH₂ (CH₂)₃ phenyl H 4-bromophenyl H H 70GPJN-78 CH₂ — 3,5-dibromophenyl H 4-bromophenyl H H 71 GPJN-79 CH₂ —3-bromophenyl H 4-iodophenyl H H 72 GPJN-80 CH₂ — 3-bromophenyl H4-chlorophenyl H H 73 GPJN-81 CH₂ CH═CH phenyl H 4-bromophenyl H H 74GPJN-82 CH₂ CH₂—O phenyl H 4-bromophenyl H H 75 GPJN-83 CH₂ CH₂—S phenylH 4-bromophenyl H H 76 GPJN-84 CH₂ — 3-bromophenyl H 3,4-dichlorophenylH H 77 GPJN-85 CH₂ (CH₂)₄ phenyl H 4-bromophenyl H H 78 GPJN-86 CH₂ —5-bromo-2-thienyl H 4-bromophenyl H H 79 GPJN-87 CH₂ — 3- H4-bromophenyl H H (trifluoromethyl)phenyl 80 GPJN-88 CH₂ — phenyl H4-(trifluoromethoxy)phenyl H H 81 GPJN-89 CH₂ — 2,3,6-trifluorophenyl H4-bromophenyl H H 82 GPJN-90 CH₂ — 2,5-difluorophenyl H 4-bromophenyl HH 83 GPJN-91 CH₂ — phenyl H 4-bromophenyl H Br 84 GPJN-94 CH₂ — phenyl H4-carboxyphenyl H H 85 GPJN-95 CH₂ — phenyl CH 4-bromophenyl H H 86GPJN-96 CH₂ — phenyl Cl 4-bromophenyl H H 87 GPJN-98 (CH₂)₂ (CH₂)₁phenyl H phenyl H H 88 GPJN-99 (CH₂)₃ — 3-bromophenyl H phenyl H H 89GPJN-100 O—CH₂—CH₂ — 3-bromophenyl H phenyl H H 90 GPJN-103 CH₂ — phenylH 4-bromophenyl H Cl 91 GPJN-104 CH₂ — phenyl H 4-bromophenyl H CH₃ 92GPJN-105 CH₂ — 2-fluorophenyl H phenyl H H 93 GPJN-106 CH₂ —2-fluorophenyl H 2-methylphenyl H H 94 GPJN-107 CH₂ — 2-fluorophenyl H3-methylphenyl H H 95 GPJN-108 CH₂ — 2-fluorophenyl H 4-methylphenyl H H96 GPJN-109 CH₂ — phenyl CH₃ 4-bromophenyl H H 97 GPJN-110 CH₂ —2-fluorophenyl H 4-phenyl-phenyl H H 98 GPJN-111 CH₂ CH₂—S phenyl H4-phenyl-phenyl H H 99 GPJN-112 CH₂ — 2-fluorophenyl H 4-chlorophenyl HH 100 GPJN-113 CH₂ — 2-fluorophenyl H 4-iodophenyl H H 101 GPJN-114 CH₂— 2-fluorophenyl H 4-(1,1-dimethylethyl)phenyl H H 102 GPJN-115 CH₂ —1-naphtalenyl H 4-phenyl-phenyl H H 103 GPC-10 CH₂ — 2,6-difluorophenylH 3,4-dichlorophenyl H H 104 GPC-11 CH₂ — 3-fluorophenyl H2,4-difluorophenyl H H 105 GPC-12 CH₂ — 2,3,6-trifluorophenyl H2,4-difluorophenyl H H 106 GPC-13 CH₂ — 2,5-difluorophenyl H2,4-difluorophenyl H H

Part A Example 1 Preparation of2-(2,6-Difluorophenyl)-1(3)H-imidazo[4,5-c]pyridine

A mixture of 3,4-diaminopyridine (2.00 g), 2,6-difluorobenzoic acid (1equivalent) and polyphosphoric acid (50 g) was heated at 180° C. for 4 hwith stirring. Then the mixture was cooled to ambient temperature andpoured into ice/water. The resulting mixture was neutralized by additionof solid Na₂CO₃. The crude product was collected by filtration, washedwith water and dried. It was used in the next step without furtherpurification.

Recrystallized from water; brownish crystals; mp: 189-190° C.; yield:60%; ¹H NMR (200 MHz, DMSO-d6) δ 13.20 (br s, 1H, NH), 9.04 (br s, 1H,H4), 8.37 (br d, 1H, H6, J=5.4 Hz), 7.76-7.61 (m, 2H, H7/4′), 7.42-7.30(m, 2H, H3′/5′).

Example 2 Preparation of 2-Phenyl-1(3)H-imidazo[4,5-c]pyridine (GPJN-10)

A mixture of 3,4-diaminopyridine (2.00 g), benzoic acid (1 equivalent)and polyphosphoric acid (50 g) was heated at 190° C. for 3 h withstirring. Then the mixture was cooled to ambient temperature and pouredinto ice/water. The resulting mixture was neutralized by addition ofsolid Na₂CO₃. The crude product was collected by filtration, washed withwater and dried. It was used in the next step without furtherpurification.

Recrystallized from water; off-white crystals; mp: 229-230° C.; yield:96%; ¹H NMR (200 MHz, DMSO-d₆) δ 8.95 (d, 1H, H4, J=1.0 Hz), 8.31 (d,1H, H6, J=5.4 Hz), 8.28-8.17 (m, 2H, arom. H), 7.64-7.50 (m, 4H, arom.H).

Example 3 Preparation of2-(2,6-Difluorophenyl)-5-[(2,6-difluorophenyl)methyl]-5H-imidazo[4,5-c]pyridine(GPRTI-8)

2-(2,6-Difluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.500 g) wasdissolved in dry DMF (5 mL) and the resulting solution was cooled to 0°C. Aqueous 50% sodium hydroxide (1.5 equivalents) was added and themixture was stirred for 15 min. Then 2,6-difluorobenzyl bromide (1.2equivalents) was added portionwise and the resulting mixture was stirredfor 24 h at room temperature. Finally, water (50 mL) was added, theprecipitate was collected by filtration and dried to give the crudeproduct mixture.

Recrystallized from ethyl acetate; colorless crystals; mp: 195-197° C.;yield: 65%; ¹H NMR (200 MHz, DMSO-d6) δ 9.08 (br s, 1H, H4), 8.09 (dd,1H, H6, J=6.6, 1.7 Hz), 7.82 (d, 1H, H7, J=6.6 Hz), 7.63-7.46 (m, 2H,H4′/4″), 7.29-7.13 (m, 4H, H3′/5′/3″/5″), 5.87 (s, 2H, CH₂); MS (EI, 70eV) m/z 357 (M⁺, 77%), 338 (4%), 230 (11%), 127 (100%); Anal.(C₁₉H₁₁F₄N₃) calcd.: C 63.87%, H 3.10%, N 11.76%, found: C 63.83%, H3.15%, N 11.63%.

Example 4 Preparation of5-Benzyl-2-(2,6-difluorophenyl)-5H-imidazo[4,5-c]pyridine (GPJN-1)

Prepared as described in example 3 from2-(2,6-difluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.500 g) and benzylbromide (0.444 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether and ethyl acetate;off-white crystals; mp: 180-181° C. (degr.); yield: 30%; ¹H NMR (200MHz, DMSO-d₆) δ 9.24 (br d, 1H, H4, J=1.5 Hz), 8.25 (dd, 1H, H6, J=6.9,1.5 Hz), 7.81 (d, 1H, H7, J=6.9 Hz), 7.60-7.33 (m, 6H,H4′/2″/3″/4″/5″/6″), 7.26-7.13 (m, 2H, H3′/5′), 5.71 (s, 2H, CH₂).

Example 5 Preparation of5-[(2,6-Difluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-3)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.500 g) and 2,6-difluorobenzylbromide (0.636 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (25 mL) and ethylacetate (60 mL); colorless crystals; mp: 214-216° C.; yield: 64%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.91 (br s, 1H, H4), 8.39-8.32 (m, 2H, arom. H),8.01 (dd, 1H, H6, J=6.9, 1.5 Hz), 7.72 (d, 1H, H7, J=6.9 Hz), 7.63-7.37(m, 4H, arom. H), 7.30-7.16 (m, 2H, H3′/5′), 5.81 (s, 2H, CH₂).

Example 6 Preparation of 5-Benzyl-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-4)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.500 g) and benzyl bromide(0.526 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (25 mL), ethylacetate (50 mL) and methanol (4 mL); colorless crystals; mp: 214-216°C.; yield: 33%; ¹H NMR (200 MHz, DMSO-d₆) δ 9.09 (d, 1H, H4, J=1.4 Hz),8.40-8.33 (m, 2H, arom. H), 8.18 (dd, 1H, H6, J=6.9, 1.4 Hz), 7.73 (d,1H, H7, J=6.9 Hz), 7.52-7.32 (m, 8H, arom. H), 5.66 (s, 2H, CH₂).

Example 7 Preparation of2-(2,6-Difluorophenyl)-5-(2-phenylethyl)-5H-imidazo[4,5-c]pyridine(GPJN-2)

Prepared as described in example 3 from2-(2,6-difluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.500 g) and2-phenylethyl bromide (0.480 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (50 mL) and ethylacetate (40 mL); off-white crystals; mp: 184-186° C. (degr.); yield:14%; ¹H NMR (200 MHz, DMSO-d₆) δ 9.02 (br d, 1H, H4, J=1.4 Hz), 8.09(dd, 1H, H6, J=6.7, 1.4 Hz), 7.74 (d, 1H, H7, J=6.7 Hz), 7.60-7.45 (m,1H, H4′), 7.34-7.12 (m, 7H, H3′/5′/2″/3″/4″/5″/6″), 4.74 (t, 2H, N—CH₂,J=7.4 Hz), 3.26 (t, 2H, CH₂, J=7.4 Hz).

Example 8 Preparation of2-Phenyl-5-(3-phenylpropyl)-5H-imidazo[4,5-c]pyridine (GPJN-14)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and1-bromo-3-phenylpropane (0.367 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (7 mL); off-white crystals; mp: 44-46° C.; yield: 44%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.95 (d, 1H, H4, J=1.4 Hz), 8.40-8.33 (m, 2H, arom.H), 8.09 (dd, 1H, H6, J=6.8, 1.4 Hz), 7.71 (d, 1H, H7, J=6.8 Hz),7.52-7.13 (m, 8H, arom. H), 4.84 (t, 2H, N—CH₂, J=7.2 Hz), 2.65-2.57 (m,2H, CH₂), 2.31-2.16 (m, 2H, CH₂).

Example 9 Preparation of5-[(2-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-7)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 2-chlorobenzylchloride (0.297 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (25 mL) and ethylacetate (65 mL); colorless crystals; mp: 224-225° C.; yield: 52%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.99 (d, 1H, H4, J=1.6 Hz), 8.40-8.33 (m, 2H, arom.H), 8.10 (dd, 1H, H6, J=6.7, 1.6 Hz), 7.75 (d, 1H, H7, J=6.7 Hz),7.59-7.34 (m, 6H, arom. H), 7.18-7.12 (m, 1H, arom. H), 5.80 (s, 2H,CH₂).

Example 10 Preparation of5-[(3-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-8)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 3-chlorobenzylbromide (0.379 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (27 mL); colorless crystals; mp: 210-212° C.; yield: 54%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.12 (d, 1H, H4, J=1.5 Hz), 8.39-8.32 (m, 2H, arom.H), 8.20 (dd, 1H, H6, J=6.7, 1.5 Hz), 7.74 (d, 1H, H7, J=6.7 Hz),7.61-7.38 (m, 7H, arom. H), 5.66 (s, 2H, CH₂).

Example 11 Preparation of5-[(4-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-9)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 4-chlorobenzylchloride (0.297 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (24 mL); colorless crystals; mp: 211-212° C.; yield: 55%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.09 (d, 1H, H4, J=1.5 Hz), 8.40-8.33 (m, 2H, arom.H), 8.17 (dd, 1H, H6, J=6.9, 1.5 Hz), 7.73 (d, 1H, H7, J=6.9 Hz),7.52-7.40 (m, 7H, arom. H), 5.66 (s, 2H, CH₂).

Example 12 Preparation of5-[(2-Methoxyphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-11)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 2-methoxybenzylchloride (0.288 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (30 mL); colorless crystals; mp: 182-184° C.; yield: 60%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.94 (d, 1H, H4, J=1.6 Hz), 8.39-8.32 (m, 2H, arom.H), 8.08 (dd, 1H, H6, J=6.7, 1.6 Hz), 7.69 (d, 1H, H7, J=6.7 Hz),7.51-7.29 (m, 5H, arom. H), 7.10-6.94 (m, 2H, arom. H), 5.61 (s, 2H,CH₂), 3.84 (s, 3H, OCH₃).

Example 13 Preparation of5-[(3-Methoxyphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-12)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 3-methoxybenzylchloride (0.288 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (23 mL); colorless crystals; mp: 157-158° C.; yield: 62%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.10 (d, 1H, H4, J=1.7 Hz), 8.40-8.33 (m, 2H, arom.H), 8.18 (dd, 1H, H6, J=6.7, 1.7 Hz), 7.72 (d, 1H, H7, J=6.7 Hz),7.52-7.27 (m, 4H, arom. H), 7.10-6.89 (m, 3H, arom. H), 5.61 (s, 2H,CH₂), 3.75 (s, 3H, OCH₃).

Example 14 Preparation of5-[(4-Methoxyphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-13)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 4-methoxybenzylchloride (0.288 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (31 mL); colorless crystals; mp: 211-212° C.; yield: 52%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.07 (d, 1H, H4, J=1.5 Hz), 8.39-8.32 (m, 2H, arom.H), 8.16 (dd, 1H, H6, J=6.9, 1.5 Hz), 7.70 (d, 1H, H7, J=6.9 Hz),7.51-7.37 (m, 5H, arom. H), 6.99-6.92 (AA′BB′, 2H, arom. H), 5.57 (s,2H, CH₂), 3.73 (s, 3H, OCH₃).

Example 15 Preparation of5-[(2-Methylphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-20)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 2-methylbenzylchloride (0.259 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (44 mL); colorless crystals; mp: 223-224° C.; yield: 60%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.93 (d, 1H, H4, J=1.6 Hz), 8.41-8.33 (m, 2H, arom.H), 8.04 (dd, 1H, H6, J=6.7, 1.6 Hz), 7.75 (d, 1H, H7, J=6.7 Hz),7.53-7.15 (m, 5H, arom. H), 6.92 (br d, 1H, arom. H, J=7.0 Hz), 5.73 (s,2H, CH₂), 2.32 (s, 3H, CH₃).

Example 16 Preparation of5-[(3-Methylphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-21)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 3-methylbenzylchloride (0.259 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (15 mL); colorless crystals; mp: 183-185° C.; yield: 46%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.08 (d, 1H, H4, J=1.5 Hz), 8.40-8.33 (m, 2H, arom.H), 8.16 (dd, 1H, H6, J=6.7, 1.5 Hz), 7.72 (d, 1H, H7, J=6.7 Hz),7.52-7.14 (m, 7H, arom. H), 5.61 (s, 2H, CH₂), 2.29 (s, 3H, CH₃).

Example 17 Preparation of5-[(4-Methylphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-15)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 4-methylbenzylchloride (0.259 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (32 mL); colorless crystals; mp: 206-208° C.; yield: 57%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.07 (d, 1H, H4, J=1.5 Hz), 8.39-8.32 (m, 2H, arom.H), 8.15 (dd, 1H, H6, J=6.7, 1.5 Hz), 7.71 (d, 1H, H7, J=6.7 Hz),7.52-7.17 (m, 7H, arom. H), 5.60 (s, 2H, CH₂), 2.28 (s, 3H, CH₃).

Example 18 Preparation of5-[(2-Fluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-17)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 2-fluorobenzylbromide (0.349 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (37 mL); colorless crystals; mp: 209-211° C.; yield: 67%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.01 (br s, 1H, H4), 8.41-8.33 (m, 2H, arom. H),8.06 (dd, 1H, H6, J=6.8, 1.6 Hz), 7.74 (d, 1H, H7, J=6.8 Hz), 7.52-7.21(m, 7H, arom. H), 5.76 (s, 2H, CH₂).

Example 19 Preparation of5-[(3-Fluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-18)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 3-fluorobenzylbromide (0.349 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (34 mL); colorless crystals; mp: 228-230° C.; yield: 55%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.12 (d, 1H, H4, J=1.5 Hz), 8.41-8.33 (m, 2H, arom.H), 8.20 (dd, 1H, H6, J=6.7, 1.5 Hz), 7.74 (d, 1H, H7, J=6.7 Hz),7.52-7.15 (m, 7H, arom. H), 5.67 (s, 2H, CH₂).

Example 20 Preparation of5-[(4-Fluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-19)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 4-fluorobenzylchloride (0.267 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (19 mL); colorless crystals; mp: 205-206° C.; yield: 56%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.11 (d, 1H, H4, J=1.7 Hz), 8.40-8.33 (m, 2H, arom.H), 8.18 (dd, 1H, H6, J=6.8, 1.7 Hz), 7.73 (d, 1H, H7, J=6.8 Hz),7.61-7.37 (m, 5H, arom. H), 7.30-7.18 (m, 2H, arom. H), 5.64 (s, 2H,CH₂).

Example 21 Preparation of5-[[4-(1,1-Dimethylethyl)phenyl]methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-16)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 4-tert-butylbenzylbromide (0.419 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (23 mL); colorless crystals; mp: 213-215° C.; yield: 49%; ¹H NMR(200 MHz, DMSO4) δ 9.07 (d, 1H, H4, J=1.6 Hz), 8.39-8.33 (m, 2H, arom.H), 8.17 (dd, 1H, H6, J=6.7, 1.6 Hz), 7.71 (d, 1H, H7, J=6.7 Hz),7.53-7.35 (m, 7H, arom. H), 5.61 (s, 2H, CH₂), 1.24 (s, 9H, (CH₃)₃).

Example 22 Preparation of5-[(4-Bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-22)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 4-bromobenzylbromide (0.461 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (26 mL); colorless crystals; mp: 212-214° C.; yield: 45%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.09 (br s, 1H, H4), 8.40-8.33 (m, 2H, arom. H),8.17 (dd, 1H, H6, J=6.8, 1.5 Hz), 7.73 (d, 1H, H7, J=6.8 Hz), 7.64-7.58(AA′BB′, 2H, arom. H), 7.52-7.37 (m, 5H, arom. H), 5.64 (s, 2H, CH₂).

Example 23 Preparation of4-[(2-Phenyl-5H-imidazo[4,5-c]pyridin-5-yl)methyl]-benzonitrile(GPJN-23)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and4-bromomethyl-benzonitrile (0.362 g, 1.2 equivalents).

Recrystallized twice from a mixture of diisopropyl ether (10 mL) andethyl acetate (25 mL); pale orange crystals; mp: 93° C. (degr.); yield:34%; ¹H NMR (200 MHz, DMSO-d₆) δ 9.10 (d, 1H, H4, J=1.5 Hz), 8.40-8.33(m, 2H, arom. H), 8.18 (dd, 1H, H6, J=6.9, 1.5 Hz), 7.91-7.85 (AA′BB′,2H, arom. H), 7.75 (d, 1H, H7, J=6.9 Hz), 7.61-7.55 (AA′BB′, 2H, arom.H), 7.52-7.37 (m, 3H, arom. H), 5.77 (s, 2H, CH₂).

Example 24 Preparation of2-Phenyl-5-[[4-(trifluoromethyl)phenyl]methyl]-5H-imidazo[4,5-c]pyridine(GPJN-24)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and4-(trifluoromethyl)benzyl bromide (0.441 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (20 mL); colorless crystals; mp: 230-232° C.; yield: 50%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.12 (d, 1H, H4, J=1.6 Hz), 8.40-8.33 (m, 2H, arom.H), 8.19 (dd, 1H, H6, J=6.9, 1.6 Hz), 7.81-7.73 (m, 3H, arom. H),7.65-7.59 (AA′BB′, 2H, arom. H), 7.53-7.38 (m, 3H, arom. H), 5.78 (s,2H, CH₂).

Example 25 Preparation of5-[(4-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridinehydrochloride (GPJN-9×HCl)

98 mg of 5-(4-chloro-benzyl)-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-9)were dissolved in dry dichloromethane (18 mL) and to this solution wasadded one equivalent of HCl (1M in diethyl ether). After 2 hours theprecipitate was collected by filtration and dried to give 70% of thehydrochloride; colorless crystals; mp:147-148° C. (degr.).

Example 26 Preparation of5-[(5-Chloro-2-thienyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-25)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and2-chloro-5-chloromethyl-thiophene (0.308 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (50 mL); off-white crystals; mp: 215-216° C.; yield: 39%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.07 (d, 1H, H4, J=1.5 Hz), 8.40-8.33 (m, 2H, arom.H), 8.19 (dd, 1H, H6, J=6.8, 1.5 Hz), 7.74 (d, 1H, H7, J=6.8 Hz),7.55-7.37 (m, 3H, arom. H), 7.28 (d, 1H, thiophene-H, J=3.8 Hz), 7.08(d, 1H, thiophene-H, J=3.8 Hz), 5.81 (s, 2H, CH₂).

Example 27 Preparation of5-(2-Naphthalenylmethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-26)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and2-bromomethyl-naphthalene (0.408 g, 1.2 equivalents).

Recrystallized from a mixture of ethyl acetate (20 mL) and ethanol (8mL); colorless crystals; mp: 267° C.; yield: 36%; ¹H NMR (200 MHz,DMSO-d₆) δ 9.17 (d, 1H, H4, J=1.7 Hz), 8.40-8.33 (m, 2H, arom. H), 8.23(dd, 1H, H6, J=6.7, 1.7 Hz), 7.99-7.87 (m, 4H, arom. H), 7.74 (d, 1H,H7, J=6.7 Hz), 7.60-7.37 (m, 6H, arom. H), 5.84 (s, 2H, CH₂).

Example 28 Preparation of2-Phenyl-5-(4-phenylbutyl)-5H-imidazo[4,5-c]pyridine (GPJN-27)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and1-chloro-4-phenylbutane (0.311 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (11 mL); colorless crystals; mp: 119-120° C.; yield: 53%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.95 (d, 1H, H4, J=1.4 Hz), 8.40-8.33 (m, 2H, arom.H), 8.07 (dd, 1H, H6, J=6.8, 1.4 Hz), 7.70 (d, 1H, H7, J=6.8 Hz),7.52-7.37 (m, 3H, arom. H), 7.31-7.10 (m, 5H, arom. H), 4.46 (t, 2H,CH₂, J=7.1 Hz), 2.62 (t, 2H, CH₂, J=7.6 Hz), 2.00-1.85 (m, 2H, CH₂),1.63-1.46 (m, 2H, CH₂).

Example 29 Preparation of5-(3-Methyl-2-butenyl)-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-28)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and4-bromo-2-methylbut-2-ene (0.275 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (11 mL); off-white crystals; mp: 162-163° C.; yield: 58%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.86 (d, 1H, H4, J=1.7 Hz), 8.40-8.33 (m, 2H, arom.H), 7.99 (dd, 1H, H6, J=6.8, 1.7 Hz), 7.71 (d, 1H, H7, J=6.8 Hz),7.52-7.37 (m, 3H, arom. H), 5.57-5.47 (m, 1H, ═CH), 5.06 (br d, 2H, CH₂,J=7.4 Hz), 1.86 (br s, 3H, CH₃), 1.77 (br s, 3H, CH₃).

Example 30 Preparation of 5-Ethyl-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-29)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and ethyl iodide (0.288g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (5 mL) and ethylacetate (12 mL); colorless crystals; mp: 188° C.; yield: 22%; ¹H NMR(200 MHz, DMSO-d₄) δ 8.96 (d, 1H, H4, J=1.6 Hz), 8.40-8.33 (m, 2H, arom.H), 8.09 (dd, 1H, H6, J=6.8, 1.6 Hz), 7.71 (d, 1H, H7, J=6.8 Hz),7.52-7.36 (m, 3H, arom. H), 4.47 (q, 2H, CH₂, J=7.3 Hz), 1.52 (t, 3H,CH₃, J=7.3 Hz).

Example 31 Preparation of5-[2-[bis(1-Methylethyl)amnino)ethyl]-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-30)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g), and2-(diisopropylamino)ethyl chloride hydrochloride (0.369 g, 1.2equivalents).

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (10 mL); colorless crystals; mp: 151-152° C.; yield: 57%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.80 (d, 1H, H4, J=1.5 Hz), 8.39-8.33 (m, 2H, arom.H), 7.99 (dd, 1H, H6, J=6.8, 1.5 Hz), 7.67 (d, 1H, H7, J=6.8 Hz),7.51-7.36 (m, 3H, arom. H), 4.36 (t, 2H, CH₂, J=5.4 Hz), 3.04-2.84 (m,4H, 2×CH and CH₂), 0.78 (d, 12H, 4×CH₃, J=6.6 Hz).

Example 32 Preparation of2-Phenyl-5-(4-pyridinylmethyl)-5H-iniidazo[4,5-c]pyridine (GPJN-31)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g), and4-chloromethyl-pyridine hydrochloride (0.303 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (15 mL); colorless crystals (hygroscopic); yield: 25%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.09 (d, 1H, H4, J=1.6 Hz), 8.60-8.57 (m, 2H,pyridine-H2/6), 8.40-8.33 (m, 2H, arom. H), 8.17 (dd, 1H, H6, J=6.8, 1.6Hz), 7.67 (d, 1H, H7, J=6.8 Hz), 7.52-7.37 (m, 3H, arom. H), 7.31-7.28(m, 2H, pyridine-H3/5), 5.74 (s, 2H, CH₂).

Example 33 Preparation of2-Phenyl-5-(2-pyridinylmethyl)-5H-imidazo[4,5-c]pyridine (GPJN-34)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g), and2-chloromethyl-pyridine hydrochloride (0.303 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (17 mL); colorless crystals; mp: 102-103° C.; yield: 44%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.02 (d, 1H, H4, J=1.4 Hz), 8.53 (ddd, 1H,pyridine-H6, J=4.7, 1.7, 0.8 Hz), 8.40-8.33 (m, 2H, arom. H), 8.13 (dd,1H, H6, J=6.8, 1.4 Hz), 7.90-7.82 (m, 1H, pyridine-H4), 7.72 (d, 1H, H7,J=6.8 Hz), 7.52-7.33 (m, 5H, arom. H), 5.79 (s, 2H, CH₂).

Example 34 Preparation of2-Phenyl-5-(3-pyridinylmethyl)-5H-imidazo[4,5-c]pyridine (GPJN-35)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g), and3-chloromethyl-pyridine hydrochloride (0.303 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (41 mL); off-white crystals; mp: 53° C. (degr.); yield: 46%; ¹HNMR (200 MHz, DMSO-d₆) δ 9.14 (d, 1H, H4, J=1.6 Hz), 8.76 (br d, 1H,pyridine-H2), 8.57 (dd, 1H, pyridine-H6, J=4.8, 1.6 Hz), 8.40-8.33 (m,2H, arom. H), 8.22 (dd, 1H, H6, J=6.8, 1.6 Hz), 7.90-7.84 (m, 1H,pyridine-H4), 7.74 (d, 1H, H7, J=6.8 Hz), 7.52-7.38 (m, 45H, arom. H),5.71 (s, 2H, CH₂).

Example 35 Preparation of5-([1,1′-Biphenyl]-4-ylmethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-32)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and4-chloromethyl-biphenyl (0.374 g, 1.2 equivalents).

Recrystallized from a mixture of ethyl acetate (50 mL) and ethanol (1.5mL); colorless crystals; mp: 247-248° C.; yield: 65%; ¹H NMR (200 MHz,DMSO-d₆) δ 9.14 (d, 1H, H4, J=1.4 Hz), 8.40-8.33 (m, 2H, arom. H), 8.22(dd, 1H, H6, J=6.8, 1.4 Hz), 7.75 (d, 1H, H7, J=6.8 Hz), 7.72-7.30 (m,12H, arom. H), 5.71 (s, 2H, CH₂).

Example 36 Preparation of2-Phenyl-5-(1-phenylethyl)-5H-imidazo[4,5-c]pyridine (GPJN-33)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and 1-phenylethylbromide (0.341 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (40 mL); colorless crystals; mp: 190-192° C.; yield: 57%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.13 (d, 1H, H4, J=1.6 Hz), 8.39-8.33 (m, 2H, arom.H), 8.19 (dd, 1H, H6, J=6.7, 1.6 Hz), 7.70 (d, 1H, H7, J=6.7 Hz),7.53-7.31 (m, 8H, arom. H), 6.01 (q, 1H, CH, J=7.0 Hz), 2.04 (d, 3H,CH₃, J=7.0 Hz).

Example 37 Preparation of5-(1-Naphthalenylmethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-36)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and1-chloromethyl-naphthalene (0.326 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (45 mL); colorless crystals; mp: 191° C.; yield: 73%; ¹H NMR(200 MHz, DMSO-d,) δ 9.08 (d, 1H, H4, J=1.5 Hz), 8.39-8.33 (m, 2H, arom.H), 8.23-8.15 (m, 2H, arom. H), 7.75 (d, 1H, H7, J=6.8 Hz), 7.68-7.37(m, 6H, arom. H), 7.25 (br d, 1H, arom. H, J=6.6 Hz), 6.22 (s, 2H, CH₂).

Example 38 Preparation of5-(Cyclohexylmethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-37)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and cyclohexylmethylbromide (0.327 g, 1.2 equivalents) with heating at 80° C.

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (14 mL); colorless crystals; mp: 188-189° C.; yield: 36%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.89 (d, 1H, H4, J=1.5 Hz), 8.39-8.33 (m, 2H, arom.H), 8.03 (dd, 1H, H6, J=6.6, 1.5 Hz), 7.69 (d, 1H, H7, J=6.6 Hz),7.52-7.37 (m, 3H, arom. H), 4.28 (d, 2H, CH₂, J=7.4 Hz), 2.02-0.92 (m,11H, cyclohexyl H).

Example 39 Preparation of5-(3-Methylbutyl)-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-38)

Prepared as described in example 3 from2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and1-bromo-3-methylbutane (0.279 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (17 mL); colorless crystals; mp: 207° C.; yield: 37%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.96 (d, 1H, H4, J=1.5 Hz), 8.40-8.34 (m, 2H, arom.H), 8.09 (dd, 1H, H6, J=6.8, 1.5 Hz), 7.70 (d, 1H, H7, J=6.8 Hz),7.52-7.37 (m, 3H, arom. H), 4.45 (t, 2H, CH₂, J=7.4 Hz), 1.87-1.75 (m,2H, CH₂), 1.53 hept, 1H, CH, J=6.6 Hz), 0.94 (d, 6H, (CH₃)₂).

Example 40 Preparation of2-(2,6-Difluorophenyl)-5-[(4-fluorophenyl)methyl]-5H-imidazo[4,5-c]pyridine(GPJN-39)

Prepared as described in example 3 from2-(2,6-Difluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and4-fluorobenzyl chloride (0.225 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (10 mL); off-white crystals; mp: 104-105° C.; yield: 48%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.26 (d, 1H, H4, J=1.4 Hz), 8.26 (dd, 1H, H6,J=6.8, 1.4 Hz), 7.81 (d, 1H, H7, J=6.8 Hz), 7.61-7.45 (m, 3H, arom. H),7.30-7.13 (m, 4H, arom. H), 5.69 (s, 2H, CH₂).

Example 41 Preparation of2-(2,6-Difluorophenyl)-5-[(2,4-difluorophenyl)methyl]-5H-imidazo[4,5-c]pyridine(GPJN-40)

Prepared as described in example 3 from2-(2,6-difluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and2,4-difluorobenzyl bromide (0.322 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (8 mL); off-white crystals; mp: 186-188° C.; yield: 29%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.16 (br s, 1H, H4), 8.18 (dd, 1H, H6, J=6.8, 1.3Hz), 7.82 (d, 1H, H7, J=6.8 Hz), 7.64-7.11 (m, 6H, arom. H), 5.78 (s,2H, CH₂).

Example 42 Preparation of2-(2,6-Difluorophenyl)-5-[(2,4,6-trifluorophenyl)methyl]-5H-imidazo[4,5-c]pyridine(GPJN-41)

Prepared as described in example 3 from2-(2,6-difluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.200 g) and2,4,6-trifluorobenzyl bromide (0.234 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (8 mL); off-white crystals; mp: 186-187° C.; yield: 26%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.06 (br s, 1H, H4), 8.08 (dd, 1H, H6, J=6.8, 1.6Hz), 7.81 (d, 1H, H7, J=6.8 Hz), 7.61-7.46 (m, 1H, H4′), 7.42-7.13 (m,4H, H3′/5′/3″/5″), 5.82 (s, 2H, CH₂).

Example 43 Preparation of5-[(4-Bromophenyl)methyl]-2-ethyl-5H-imidazo[4,5-c]pyridine (GPJN-48)

A mixture of 3,4-diaminopyridine (1.00 g), propionic acid (1 equivalent)and polyphosphoric acid (25 g) was heated at 150° C. for 1 h and then at190° C. for 2 h with stirring. Then the mixture was cooled to ambienttemperature and poured into ice/water. The resulting mixture was madealkaline by addition of 2N NaOH and extracted with ethyl acetate (100mL) six times. The combined organic phases were dried (Na₂SO₄) andevaporated to give the crude product, which was recrystallized fromethyl acetate (100 mL) to give 56% of2-ethyl-1(3)H-imidazo[4,5-c]pyridine as a white powder.

2-Ethyl-1(3)H-imidazo[4,5-c]pyridine (0.245 g) was dissolved in dry DMF(6 mL) and the resulting solution was cooled to 0° C. Aqueous 33% sodiumhydroxide (1.5 equivalents) was added and the mixture was stirred for 15min. Then 4-bromobenzyl bromide (1.2 equivalents) was added portionwiseand the resulting mixture was stirred for 24 h at room temperature.Finally, water (50 mL) was added, the precipitate was collected byfiltration and dried to give the crude product mixture.

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (6 mL); off-white crystals; mp: 149-151° C. (degr.); yield: 47%;¹H NMR (200 MHz, DMSO-d₆) δ 8.89 (d, 1H, H4, J=1.5 Hz), 8.09 (dd, 1H,H6, J=6.8, 1.5 Hz), 7.62-7.54 (m, 3H, arom. H), 7.39-7.32 (AA′BB′, 2H,arom. H), 5.60 (s, 2H, CH₂), 2.84 (q, 2H, CH₂, J=7.5 Hz), 1.30 (t, 3H,CH₃, J=7.5 Hz).

Example 44 Preparation of5-[(4-Bromophenyl)methyl]-2-(2-chlorophenyl)-5H-imidazo[4,5-c]pyridine(GPJN-54)

A mixture of 3,4-diaminopyridine (1.00 g), 2-chlorobenzoic acid (1equivalent) and polyphosphoric acid (25 g) was heated at 190° C. for 3 hwith stirring. Then the mixture was cooled to ambient temperature andpoured into ice water. The resulting mixture was made alkaline byaddition of 2N NaOH and the resulting precipitate was collected byfiltration and dried. The crude product was recrystallized from amixture of water (100 mL) and ethanol (17 mL) to give 67% of2-(2-chlorophenyl)-1(3)H-imidazo[4,5-c]pyridine as an off-white powder.

2-(2-Chlorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.383 g) was dissolvedin dry DMF (10 mL) and the resulting solution was cooled to 0° C.Aqueous 33% sodium hydroxide (1.5 equivalents) was added and the mixturewas stirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (25 mL); pale orange powder; mp: 190-192° C.; yield: 33%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.21 (d, 1H, H4, J=1.6 Hz), 8.22 (dd, 1H, H6,J=6.8, 1.6 Hz), 8.09-8.02 (m, 1H, arom. H), 7.80 (d, 1H, H7, J=6.8 Hz),7.65-7.51 (m, 3H, arom. H), 7.46-7.38 (m, 4H, arom. H), 5.67 (s, 2H,CH₂).

Example 45 Preparation of5-[(4-Bromophenyl)methyl]-2-(3-chlorophenyl)-5H-imidazo[4,5-c]pyridine(GPJN-55)

A mixture of 3,4-diaminopyridine (1.00 g), 3-chlorobenzoic acid (1equivalent) and polyphosphoric acid (25 g) was heated at 190° C. for 3 hwith stirring. Then the mixture was cooled to ambient temperature andpoured into ice/water. The resulting mixture was made alkaline byaddition of 2N NaOH and the resulting precipitate was collected byfiltration and dried. The crude product was recrystallized from amixture of water (100 mL) and ethanol (180 mL) to give 63% of2-(3-chlorophenyl)-1(3)H-imidazo[4,5-c]pyridine as a white powder.

2-(3-Chlorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.383 g) was dissolvedin dry DMF (10 mL) and the resulting solution was cooled to 0° C.Aqueous 33% sodium hydroxide (1.5 equivalents) was added and the mixturewas stirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (45 mL); colorless powder; mp: 155-157° C.; yield: 42%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.16 (d, 1H, H4, J=1.5 Hz), 8.35-8.28 (m, 2H, arom.H), 8.20 (dd, 1H, H6, J=6.9, 1.5 Hz), 7.80 (d, 1H, H7, J=6.9 Hz),7.64-7.38 (m, 6H, arom. H), 5.66 (s, 2H, CH₂).

Example 46 Preparation of5-[(4-Bromophenyl)methyl]-2-(4-chlorophenyl)-5H-imidazo[4,5-c]pyridine(GPJN-56)

A mixture of 3,4-diaminopyridine (1.00 g), 4-chlorobenzoic acid (1equivalent) and polyphosphoric acid (25 g) was heated at 190° C. for 3 hwith stirring. Then the mixture was cooled to ambient temperature andpoured into ice/water. The resulting mixture was made alkaline byaddition of 2N NaOH and the resulting precipitate was collected byfiltration and dried. The crude product was recrystallized from amixture of water (100 mL) and ethanol (110 mL) to give 47% of2-(4-chlorophenyl)-1(3)H-imidazo[4,5-c]pyridine as a colorless powder.

2-(4-Chlorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.383 g) was dissolvedin dry DMF (10 mL) and the resulting solution was cooled to 0° C.Aqueous 33% sodium hydroxide (1.5 equivalents) was added and the mixturewas stirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (25 mL); off-white powder; mp: 214-215° C.; yield: 67%; ¹H NMR(200 MHz, DMSO-₆) δ 9.13 (d, 1H, H4, J=1.6 Hz), 8.39-8.32 (AA′BB′, 2H,arom. H), 8.18 (dd, 1H, H6, J=6.9, 1.6 Hz), 7.64-7.58 (AA′BB′, 2H, arom.H), 7.56-7.49 (AA′BB′, 2H, arom. H), 7.44-7.38 (AA′BB′, 2H, arom. H),5.65 (s, 2H, CH₂).

Example 47 Preparation of5-[(4-Bromophenyl)methyl]-2-(2-pyridinyl)-5H-imidazo[4,5-c]pyridine(GPJN-58)

A mixture of 3,4-diaminopyridine (1.00 g), picolinic acid (1 equivalent)and polyphosphoric acid (25 g) was heated at 190° C. for 3 h withstirring. Then the mixture was cooled to ambient temperature and pouredinto ice/water. The resulting mixture was made alkaline by addition ofsolid NaOH and the resulting precipitate was collected by filtration anddried. The crude product was recrystallized from a mixture of water (50mL) and ethanol (7 mL) to give 55% of2-(2-pyridyl)-1(3)H-imidazo[4,5-c]pyridine as an off-white powder.

2-(2-Pyridyl)-1(3)H-imidazo[4,5-c]pyridine (0.327 g) was dissolved indry DMF (10 mL) and the resulting solution was cooled to 0° C. Aqueous33% sodium hydroxide (1.5 equivalents) was added and the mixture wasstirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from a mixture of ethyl acetate (75 mL) and ethanol (10mL); pale brown crystals; mp: 256-258° C.; yield: 43%; ¹H NMR (200 MHz,DMSO-d,) δ 9.21 (d, 1H, H4, J=1.4 Hz), 8.68 (ddd, 1H, pyridine-H6), 8.40(ddd, 1H, pyridine-H), 8.20 (dd, 1H, H6, J=6.8, 1.4 Hz), 7.89 (ddd, H,pyridine-H), 7.79 (d, 1H, H7, J=6.8 Hz), 7.65-7.58 (AA′BB′, 2H, arom.H), 7.45-7.37 (m, 3H, arom. H), 5.68 (s, 2H, CH₂).

Example 48 Preparation of5-[(4-Bromophenyl)methyl]-2-(3-pyridinyl)-5H-imidazo[4,5-c]pyridine(GPJN-57)

A mixture of 3,4-diaminopyridine (1.00 g), nicotinic acid (1 equivalent)and polyphosphoric acid (25 g) was heated at 190° C. for 3 h withstirring. Then the mixture was cooled to ambient temperature and pouredinto ice/water. The resulting mixture was made alkaline by addition ofsolid NaOH and the resulting solution was evaporated. The residue wasextracted twice with ethyl acetate (2×200 mL) and the combined organicphases were dried (Na₂SO₄) and evaporated. The crude product, thusobtained, was recrystallized from a mixture of ethyl acetate (50 mL) andethanol (13 mL) to give 34% of2-(3-pyridyl)-1(3)H-imidazo[4,5-c]pyridine as an off-white powder.

2-(3-Pyridyl)-1(3)H-imidazo[4,5-c]pyridine (0.327 g) was dissolved indry DMF (10 mL) and the resulting solution was cooled to 0° C. Aqueous33% sodium hydroxide (1.5 equivalents) was added and the mixture wasstirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from a mixture of diisopropyl ether (10 mL), ethylacetate (75 mL) and ethanol (20 mL); pale yellow powder; mp: 270-272°C.; yield: 40%; ¹H NMR (200 MHz, DMSO-d₆) δ 9.49 (m, 1H, pyridine-H2),9.18 (d, 1H, H4, J=1.5 Hz), 8.65-8.60 (m, 2H, arom. H), 8.21 (dd, 1H,H6, J=6.8, 1.5 Hz), 7.79 (d, 1H, H7, J=6.8 Hz), 7.65-7.58 (AA′BB′, 2H,arom. H), 7.54-7.38 (m, 3H, arom. H), 5.66 (s, 2H, CH₂).

Example 49 Preparation of5-[(4-Bromophenyl)methyl]-2-(4-pyridinyl)-5H-imidazo[4,5-c]pyridine(GPJN-49)

A mixture of 3,4-diaminopyridine (1.00 g), isonicotinic acid (1equivalent) and polyphosphoric acid (25 g) was heated at 190° C. for 3 hwith stirring. Then the mixture was cooled to ambient temperature andpoured into ice/water. The resulting mixture was made alkaline byaddition of solid NaOH and the resulting precipitate was collected byfiltration and dried. The crude product was recrystallized from water(55 mL) to give 84% of 2-(4-pyridyl)-1(3)H-imidazo[4,5-c]pyridine as apale orange powder.

2-(4-Pyridyl)-1(3)H-imidazo[4,5-c]pyridine (0.327 g) was dissolved indry DMF (11 mL) and the resulting solution was cooled to 0° C. Aqueous33% sodium hydroxide (1.5 equivalents) was added and the mixture wasstirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (75 mL); pale brown powder; mp: 190-194° C. (degr.); yield: 40%;¹H NMR (200 MHz, DMSO-d₆) δ 9.25 (d, 1H, H4, J=1.4 Hz), 8.70-8.67 (m,2H, pyridine-H2/6), 8.25-8.20 (m, 3H, arom. H), 7.83 (d, 1H, H7, J=6.8Hz), 7.64-7.58 (AA′BB′, 2H, arom. H), 7.45-7.39 (AA′BB′, 2H, arom. H),5.68 (s, 2H, CH₂).

Example 50 Preparation of5-[(4-Bromophenyl)methyl]-2-(2-thienyl)-5H-imidazo[4,5-c]pyridine(GPJN-53)

A mixture of 3,4-diaminopyridine (1.00 g), thiophene-2-carboxylic acid(1 equivalent) and polyphosphoric acid (25 g) was heated at 190° C. for3 h with stirring. Then the mixture was cooled to ambient temperatureand poured into ice/water. The resulting mixture was neutralized byaddition of solid NaOH and the resulting precipitate was collected byfiltration and dried. The crude product was recrystallized from amixture of water (50 mL) and ethanol (25 ml) to give 30% of2-(2-thienyl)-1(3)H-imidazo[4,5-c]pyridine as pale yellow crystals.

2-(2-Thienyl)-1(3)H-imidazo[4,5-c]pyridine (0.335 g) was dissolved indry DMF (10 mL) and the resulting solution was cooled to 0° C. Aqueous33% sodium hydroxide (1.5 equivalents) was added and the mixture wasstirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from ethyl acetate (70 mL); pale yellow powder; mp:230-231° C.; yield: 24%; ¹H NMR (200 MHz, DMSO-d₆) δ 9.01 (d, 1H, H4,J=1.5 Hz), 8.16 (dd, 1H, H6, J=6.8, 1.5 Hz), 7.81 (dd, 1H, thiophene-H,J=3.6, 1.4 Hz), 7.67 (d, 1H, H7, J=6.8 Hz), 7.64-7.57 (m, 3H, arom. H),7.43-7.37 (AA′BB′, 2H, arom. H), 5.63 (s, 2H, CH₂).

Example 51 Preparation of2-Benzyl-5-[(4-bromophenyl)methyl]-5H-imidazo[4,5-c]pyridine (GPJN-67)

A mixture of 3,4-diaminopyridine (1.00 g), phenylacetic acid (1equivalent) and polyphosphoric acid (25 g) was heated at 120° C. for 1 hand then at 150° C. for 12 h with stirring. Then the mixture was cooledto ambient temperature and poured into ice/water. The resulting mixturewas made alkaline by addition of solid NaOH and the resultingprecipitate was collected by filtration and dried. The crude product wasrecrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (76 mL) to give 57% of 2-benzyl-1(3)H-imidazo[4,5-c]pyridine asa colorless powder.

2-Benzyl-1(3)H-imidazo[4,5-c]pyridine (0.500 g) was dissolved in dry DMF(5 mL) and the resulting solution was cooled to 0° C. Aqueous 33% sodiumhydroxide (1.5 equivalents) was added and the mixture was stirred for 15min. Then 4-bromobenzyl bromide (1.2 equivalents) was added portionwiseand the resulting mixture was stirred for 24 h at room temperature.Finally, water (80 mL) was added, the precipitate was collected byfiltration and dried to give the crude product.

Recrystallized from a mixture of ethyl acetate (50 mL) and ethanol (6.5mL); pale yellow powder; mp: 232-233° C.; yield: 46%; ¹H NMR (200 z,DMSO-d₆) δ 8.94 (d, 1H, H4, J=1.4 Hz), 8.10 (dd, 1H, H6, J=6.8, 1.4 Hz),7.61-7.39 (m, 3H, arom. H), 7.38-7.10 (m, 7H, arom. H), 5.65 (s, 2H,5-CH₂), 4.17 (s, 2H, 2-CH₂).

Example 52 Preparation of5-[(4-Bromophenyl)methyl)-2-(1-naphthalenyl)-5H-imidazo[4,5-c]pyridine(GPJN-62)

A mixture of 3,4-diaminopyridine (1.00 g), 1-naphthoic acid (1equivalent) and polyphosphoric acid (25 g) was heated at 190° C. for 3hours with stirring. Then the mixture was cooled to ambient temperatureand poured into ice/water. The resulting mixture was made alkaline byaddition of solid NaOH and the resulting precipitate was collected byfiltration and dried. The crude product was recrystallized from amixture of water (100 mL) and ethanol (130 mL) to give 47% of2-(1-naphthalenyl)-I(3)H-imidazo[4,5-c]pyridine as an off-white powder.

2-(1-Naphthalenyl)-1(3)H-imidazo[4,5-c]pyridine (0.409 g) was dissolvedin dry DMF (10 mL) and the resulting solution was cooled to 0° C.Aqueous 33% sodium hydroxide (1.5 equivalents) was added and the mixturewas stirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from a mixture of diisopropyl ether (10 mL), ethylacetate (50 mL) and ethanol (5 mL); pale yellow powder; mp: 210-213° C.(degr.); yield: 22%; ¹H NMR (200 MHz, DMSO-d₆) δ 9.73 (m, 1H, arom. H),9.22 (d, 1H, H4, J=1.6 Hz), 8.52 (dd, 1H, arom. H, J=7.2, 1.4 Hz), 8.23(dd, 1H, H6, J=6.8, 1.6 Hz), 8.03-7.95 (m, 2H, arom. H), 7.83 (d, 1H,H7, J=6.8 Hz), 7.65-7.41 (m, 7H, arom. H), 5.68 (s, 2H, CH₂).

Example 53 Preparation of5-[(4-Bromophenyl)methyl]-2-(2-naphthalenyl)-5H-imidazo[4,5-c]pyridine(GPJN-63)

A mixture of 3,4-diaminopyridine (1.00 g), 2-naphthoic acid (1equivalent) and polyphosphoric acid (25 g) was heated at 190° C. for 3hours with stirring. Then the mixture was cooled to ambient temperatureand poured into ice/water. The resulting mixture was made alkaline byaddition of solid NaOH and the resulting precipitate was collected byfiltration and dried. The crude product was recrystallized from amixture of water (100 mL) and ethanol (400 mL) to give 28% of2-(2-naphthalenyl)-1(3)H-imidazo[4,5-c]pyridine as an off-white powder.

2-(2-Naphthalenyl)-1(3)H-imidazo[4,5-c]pyridine (0.409 g) was dissolvedin dry DMF (10 mL) and the resulting solution was cooled to 0° C.Aqueous 33% sodium hydroxide (1.5 equivalents) was added and the mixturewas stirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from a mixture of diisopropyl ether (20 mL) and ethylacetate (60 mL); pale orange powder; mp: 133-138° C. (degr.); yield:52%; ¹H NMR (200 MHz, DMSO-d₆) δ 9.13 (d, 1H, H4, J=1.4 Hz), 8.93 (br s,1H, arom. H), 8.51 (dd, 1H, arom. H, J=8.6, 1.6 Hz), 8.19 (dd, 1H, H6,J=6.7, 1.4 Hz), 8.10-7.90 (m, 3H, arom. H), 7.76 (d, 1H, H7, J=6.7 Hz),7.65-7.50 (m, 4H, arom. H), 7.52-7.39 (AA′BB′, 2H, arom. H), 5.67 (s,2H, CH₂).

Example 54 Preparation of5-[(4-Bromophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine(GPJN-52)

A mixture of 3,4-diaminopyridine (1.00 g), 2-fluorobenzoic acid (1equivalent) and polyphosphoric acid (25 g) was heated at 190° C. for 3 hwith stirring. Then the mixture was cooled to ambient temperature andpoured into ice/water. The resulting mixture was made alkaline byaddition of 2N NaOH and the resulting precipitate was collected byfiltration and dried. The crude product was recrystallized from amixture of water (100 mL) and ethanol (20 mL) to give 87% of2-(2-fluorophenyl)-1(3)H-imidazo[4,5-c]pyridine as an off-white powder.

2-(2-Fluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.355 g) was dissolvedin dry DMF (7 mL) and the resulting solution was cooled to 0° C. Aqueous33% sodium hydroxide (1.5 equivalents) was added and the mixture wasstirred for 15 min. Then 4-bromobenzyl bromide (1.2 equivalents) wasadded portionwise and the resulting mixture was stirred for 24 h at roomtemperature. Finally, water (80 mL) was added, the precipitate wascollected by filtration and dried to give the crude product.

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (25 mL); off-white powder; mp: 156° C.; yield: 53%; ¹H NMR (200MHz, DMSO-d₆) δ 9.18 (d, 1H, H4, J=1.6 Hz), 8.35-8.26 (m, 1H, arom. H),8.20 (dd, 1H, H6, J=6.8, 1.6 Hz), 7.78 (d, 1H, H7, J=6.8 Hz), 7.64-7.58(AA′BB′, 2H, arom. H), 7.52-7.24 (m, 5H, arom. H), 5.66 (s, 2H, CH₂).

Example 55 Preparation of5-[(4-Bromophenyl)methyl]-2-[(1E)-2-phenylethenyl]-5H-imidazo[4,5-c]pyridine(GPJN-81)

A mixture of 3,4-diaminopyridine (0.500 g) and cinnamic acid (2.036 g, 3equivalents) was heated at 160° C. for 24 h with stirring. The resultingmixture was cooled to ambient temperature and washed with diisopropylether. The remaining solid was dissolved in ethyl acetate and theresulting solution was extracted with 2N aqueous sodium hydroxidesolution. The organic phase was dried and evaporated to give 0.580 g ofa pale brown solid. Recrystallization from a mixture of diisopropylether (20 mL) and ethyl acetate (31 mL) gave 30% of2-[(1E)-2-phenylethenyl]-1(3)H-imidazo[4,5-c]pyridine as an off-whitepowder.

2-[(1E)-2-Phenylethenyl]-1(3)H-imidazo[4,5-c]pyridine (0.250 g) wasdissolved in dry DMF (3 mL) and the resulting solution was cooled to 0°C. Aqueous 33% sodium hydroxide (1.5 equivalents) was added and themixture was stirred for 15 min. Then 4-bromobenzyl bromide (1.2equivalents) was added portionwise and the resulting mixture was stirredfor 24 h at room temperature. Finally, water (30 mL) was added, theprecipitate was collected by filtration and dried to give the crudeproduct.

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (35 mL); pale brown powder; mp: 212-214° C. (degr.); yield: 27%;¹H NMR (200 MHz, DMSO-d₆) δ 9.02 (d, 1H, H4, J=1.6 Hz), 8.15 (dd, 1H,H6, J=6.6, 1.6 Hz), 7.83 (d, 1H, ═CH, J=16.2 Hz), 7.72-7.59 (m, 5H,arom. H), 7.48-7.30 (m, 6H), 5.63 (s, 2H, CH₂).

Example 56 Preparation of5-[(4-Bromophenyl)methyl]-2-[(phenylthio)methyl]-5H-imidazo[4,5-c]pyridine(GPJN-83)

A mixture of 3,4-diaminopyridine (0.500 g) and phenylthioacetic acid(2.312 g, 3 equivalents) was heated at 160° C. for 6 h with stirring.The resulting mixture was cooled to ambient temperature and washed withdiisopropyl ether. The remaining solid was dissolved in ethyl acetateand the resulting solution was extracted with 2N aqueous sodiumhydroxide solution. The organic phase was dried and evaporated to give0.520 g of a pale brown solid. Recrystallization from a mixture ofdiisopropyl ether (20 mL) and ethyl acetate (16 mL) gave 32% of2-[(phenylthio)methyl]-1(3)H-imidazo[4,5-c]pyridine as an off-whitepowder.

2-[(Phenylthio)methyl]-1(3)H-imidazo[4,5-c]pyridine (0.300 g) wasdissolved in dry DMF (5 mL) and the resulting solution was cooled to 0°C. Aqueous 33% sodium hydroxide (1.5 equivalents) was added and themixture was stirred for 15 min. Then 4-bromobenzyl bromide (1.2equivalents) was added portionwise and the resulting mixture was stirredfor 24 h at room temperature. Finally, water (50 mL) was added, theprecipitate was collected by filtration and dried to givee the crudeproduct.

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (30 mL); pale brown powder; mp: 168-170° C. (degr.); yield: 32%;¹H NMR (200 MHz, DMSO-d₆) δ 9.05 (d, 1H, H4, J=1.6 Hz), 8.16 (dd, 1H,H6, J=6.8, 1.6 Hz), 7.67 (d, 1H, H7, J=6.8 Hz), 7.63-7.56 (AA′BB′, 2H,arom. H), 7.48-7.14 (m, 6H, arom. H), 7.18-7.09 (m, 1H, arom. H), 5.63(s, 2H, N—CH₂), 4.41 (s, 2H, S—CH₂).

Example 57 Preparation of5-([1,1′-Biphenyl]-4-ylmethyl)-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine(GPJN-110)

Prepared as described in example 3 from2-(2-fluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.263 g) and4-chloromethyl-biphenyl (0.300 g, 1.2 equivalents).

Recrystallized from ethyl acetate (55 mL); colorless needles; mp: 216°C.; yield: 35%; ¹H NMR (200 MHz, DMSO-d₆) δ 9.23 (d, 1H, H4, J=1.6 Hz),8.36-8.23 (m, 2H, arom. H), 7.80 (d, 1H, H7, J=6.6 Hz), 7.73-7.24 (m,12H, arom. H), 5.73 (s, 2H, CH₂).

Example 58 Preparation of5-[(4-Chlorophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine(GPJN-112)

Prepared as described in example 3 from2-(2-fluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and4-chlorobenzyl chloride (0.272 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (25 mL); off-white crystals; mp: 167° C.; yield: 53%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.18 (d, 1H, H4, J=1.4 Hz), 8.35-8.26 (m, 1H, arom.H), 8.21 (dd, 1H, H6, J=6.6, 1.4 Hz), 7.78 (d, 1H, H7, J=6.6 Hz),7.53-7.24 (m, 7H, arom. H), 5.68 (s, 2H, CH₂).

Example 59 Preparation of2-(2-Fluorophenyl)-5-[(4-iodophenyl)methyl]-5H-imidazo[4,5-c]pyridine(GPJN-113)

Prepared as described in example 3 from2-(2-fluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and4-iodobenzyl bromide (0.501 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (25 mL); off-white crystals; mp: 181° C.; yield: 75%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.17 (d, 1H, H4, J=1.6 Hz), 8.35-8.26 (m, 1H, arom.H), 8.19 (dd, 1H, H6, J=6.6, 1.6 Hz), 7.81-7.74 (m, 3H, arom. H),7.52-7.23 (m, 5H, arom. H), 5.64 (s, 2H, CH₂).

Example 60 Preparation of5-[[4-(1,1-Dimethylethyl)phenyl]methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine(GPJN-114)

Prepared as described in example 3 from2-(2-fluorophenyl)-1(3)H-imidazo[4,5-c]pyridine (0.300 g) and4-tert-butylbenzyl bromide (0.384 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (58 mL); colorless crystals; mp: 235° C.; yield: 59%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.17 (d, 1H, H4, J=1.6 Hz), 8.35-8.26 (m, 1H, arom.H), 8.21 (dd, 1H, H6, J=6.8, 1.6 Hz), 7.77 (d, 1H, H7, J=6.8 Hz),7.52-7.24 (m, 7H, arom. H), 5.64 (s, 2H, CH₂), 1.25 (s, 9H, (CH₃)₃).

Example 61 Preparation of5-([1,1′-Biphenyl]-4-ylmethyl)-2-(1-naphthalenyl)-5H-imidazo[4,5-c]pyridine(GPJN-115)

Prepared as described in example 3 from2-(1-naphthalenyl)-1(3)H-imidazo[4,5-c]pyridine (0.303 g) and4-chloromethyl-biphenyl (0.300 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (5 mL) and ethylacetate (43 mL); off-white powder; mp: 216° C.; yield: 23%; ¹H NMR (200MHz, DMSO-d₆) δ 9.77-9.71 (m, 1H, arom. H), 9.28 (d, 1H, H4, J=1.6 Hz),8.53 (dd, 1H, arom. H, J=7.2, 1.2 Hz), 8.29 (dd, 1H, H6, J=6.6, 1.6 Hz),8.02-7.32 (m, 15H, arom. H), 5.75 (s, 2H, CH₂).

Example 62 Preparation of5-[(4-Bromophenyl)methyl]-2-(phenoxymethyl)-5H-imidazo[4,5-c]pyridine(GPJN-82)

Prepared in analogy to example 56 by using phenoxyacetic acid instead ofphenylthioacetic acid.

Recrystallized from a mixture of diisopropyl ether (10 mL) and ethylacetate (30 mL); off-white powder, mp: 168-169° C.; yield: 31%; ¹H NMR(200 MHz, DMSO-d₆) δ 9.13 (d, 1H, H4, J=1.5 Hz), 8.19 (dd, 1H, H6,J=6.8, 1.5 Hz), 7.72 (d, 1H, H7, J=6.8 Hz), 7.63-7.56 (AA′BB′, 2H, arom.H), 7.42-7.35 (AA′BB′, 2H, arom. H), 7.31-6.86 (m, 5H, arom. H), 5.65(s, 2H, N—CH₂), 5.28 (s, 2H, O—CH₂).

Example 63 Preparation of5-[(4-Bromophenyl)methyl]-4-chloro-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-96)

Prepared as described in example 3 from4-chloro-2-phenyl-1(3)H-imidazo[4,5-c]pyridine (0.425 g) and4-bromobenzyl bromide (0.270 g, 1.2 equivalents).

Purified by column chromatography (dichloromethane:methanol=20:1);colorless crystals; mp: 245-250° C.; yield: 11%; ¹H NMR (200 MHz,DMSO-d₆) δ 8.44 (d, 1H, H6, J=6.7 Hz), 8.40-8.33 (m, 2H, arom. H), 7.83(d, 1H, H7, J=6.7 Hz), 7.63-7.57 (AA′BB′, 2H, arom. H), 7.55-7.43 (m,3H, arom. H), 7.21-7.15 (AA′BB′, 2H, arom. H), 5.88 (s, 2H, CH₂).

Example 64 Preparation of5-[(4-Bromophenyl)methyl]-4-hydroxy-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-95)(=5-[(4-Bromophenyl)methyl]-1,4-dihydro-4-oxo-2-phenyl-5H-imidazo[4,5-c]pyridine)

5-[(4-Bromophenyl)methyl]-4-chloro-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-96) (see example 63) (0.200 g) was dissolved in DMF (5 mL) and 2Naqueous sodium hydroxide solution (10 mL) was added. The resultingmixture was heated at 60° C. for 24 h. Then water (50 mL) was added andthe resulting mixture was neutralized by addition of 2N HCl. Theprecipitate was collected by filtration to give the crude product.

Recrystallized from a mixture of diisopropyl ether (25 mL) and ethylacetate (23 mL); colorless powder; mp: 268-270° C.; yield: 81%; ¹H NMR(200 MHz, DMSO-d₆) δ 8.17-8.13 (m, 2H, arom. H), 7.59-7.44 (m, 6H, arom.H), 7.28-7.23 (AA′BB′, 2H, arom. H), 6.67 (br d, 2H, H7, J=6.8 Hz), 5.21(s, 2H, CH₂).

Example 65 Preparation of5-[(4-Bromophenyl)methyl]-7-chloro-2-phenyl-5H-imidazo[4,5-c]pyridine(GPJN-103)

Prepared as described in example 3 from7-chloro-2-phenyl-1(3)H-imidazo[4,5c]pyridine (0.300 g) (prepared asdescribed in example 2 from 5-chloro-3,4-diaminopyridine and benzoicacid) and 4-bromobenzyl bromide (0.240 g, 1.2 equivalents).

Recrystallized from a mixture of diisopropyl ether (10 mL), ethylacetate (35 mL) and ethanol (2 mL); off-white crystals; mp: 215-217° C.;yield: 48%; ¹H NMR (200 MHz, DMSO-₆) δ 9.17 (d, 1H, H4, J=1.2 Hz), 8.56(d, 1H, H6, J=1.2 Hz), 8.40-8.33 (m, 2H, arom. H), 7.65-7.59 (AA′BB′,2H, arom. H), 7.54-7.44 (m, 5H, arom. H), 5.65 (s, 2H, CH₂).

In analogy to the above examples, the following additional compoundswere prepared:

-   -   5-[(2-Bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-42)    -   5-[(3-Bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-43)    -   2-[(2-Phenyl-5H-imidazo[4,5-c]pyridin-5-yl)methyl]-benzonitrle        (GPJN-44)    -   3-[(2-Phenyl-5H-imidazo[4,5-c]pyridin-5-yl)methyl]-benzonitrile        (GPJN-45)    -   2-Phenyl-5-[[2-(trifluoromethyl)phenyl]methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-46)    -   2-Phenyl-5-[[3-(trifluoromethyl)phenyl]methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-47)    -   5-[(4-Bromophenyl)methyl]-2-(3-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-50)    -   5-[(4-Bromophenyl)methyl]-2-(3-fluorophenyl)-SH-imidazo[4,5-c]pyridine        (GPJN-51)    -   5-[(4-Bromophenyl)methyl]-2-(2-methylphenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-59)    -   5-[(4-Bromophenyl)methyl]-2-(3-methylphenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-60)    -   5-[(4-Bromophenyl)methyl]-2-(4-methylphenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-61)    -   5-[(4-Bromophenyl)methyl]-2-(3-methoxyphenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-64)    -   2-(3-Bromophenyl)-5-[(4-bromophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-65)    -   N,N-Dimethyl-3-[5-[(4-Bromophenyl)methyl]-5H-imidazo[4,5-c]pyridin-2-yl]-benzenamine        (GPJN-66)    -   5-[(4-Iodophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-68)    -   5-[(4-Bromophenyl)methyl]-2-(3-iodophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-69)    -   5-[(4-Bromophenyl)methyl]-2-(2-bromophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-70)    -   5-(2-Ethylbutyl)-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-72)    -   5-(2-Phenoxyethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine (GPJN-73)    -   5-[(3,4-Dichlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-74)    -   2-Phenyl-5-(3-phenyl-2-propenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-75)    -   5-[(4-Bromophenyl)methyl]-2-(2-phenylethyl)-5H-imidazo[4,5-c]pyridine        (GPJN-76)    -   5-[(4-Bromophenyl)methyl]-2-(3-phenylpropyl)-5H-imidazo[4,5-c]pyridine        (GPJN-77)    -   5-[(4-Bromophenyl)methyl]-2-(3,5-dibromophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-78)    -   2-(3-Bromophenyl)-5-[(4-iodophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-79)    -   2-(3-Bromophenyl)-5-[(4-chlorophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-80)    -   2-(3-Bromophenyl)-5-[(3,4-dichlorophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-84)    -   5-[(4-Bromophenyl)methyl]-2-(4-phenylbutyl)-5H-imidazo[4,5-c]pyridine        (GPJN-85)    -   5-[(4-Bromophenyl)methyl]-2-(5-bromo-2-thienyl)-5H-imidazo[4,5-c]pyridine        (GPJN-86)    -   5-[(4-Bromophenyl)methyl]-2-[3-(trifluoromethyl)phenyl]-5H-imidazo[4,5-c]pyridine        (GPJN-87)    -   2-Phenyl-5-[[4-(trifluoromethoxy)phenyl]methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-88)    -   5-[(4-Bromophenyl)methyl]-2-(2,3,6-trifluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-89)    -   5-[(4-Bromophenyl)methyl]-2-(2,5-difluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPJN-90)    -   7-Bromo-5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-91)    -   4-[2-Phenyl-5H-imidazo[4,5-c]pyridin-5-yl]-benzoic acid        (GPJN-94)    -   2-Benzyl-5-(2-phenylethyl)-5H-imidazo[4,5-c]pyridine (GPJN-98)    -   2-(3-Bromophenyl)-5-(3-phenylpropyl)-5H-imidazo[4,5-c]pyridine        (GPJN-99)    -   2-(3-Bromophenyl)-5-(2-phenoxyethyl)-5H-imidazo[4,5-c]pyridine        (GPJN-100)    -   5-[(4-Bromophenyl)methyl]-7-methyl-2-phenyl-5H-imidazo[4,5-c]pyridine        (GPJN-104)    -   5-Benzyl-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine (GPJN-105)    -   2-(2-Fluorophenyl)-5-[(2-methylphenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-106)    -   2-(2-Fluorophenyl)-5-[(3-methylphenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-107)    -   2-(2-Fluorophenyl)-5-[(4-methylphenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-108)    -   5-([1,1′-Biphenyl]-4-ylmethyl)-2-[(phenylthio)methyl]-5H-imidazo[4,5-c]pyridine        (GPJN-111)    -   5-[(3,4-Dichlorophenyl)methyl]-2-(2,6-difluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPC-10)    -   5-[(2,4-Difluorophenyl)methyl]-2-(3-fluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPC-11)    -   5-[(2,4-Difluorophenyl)methyl]-2-(2,3,6-trifluorophenyl)-5H-imidazo[4,5-c]pyridine        (GPC-12)    -   2-(2,5-Difluorophenyl)-5-[(2,4-difluorophenyl)methyl]-5H-imidazo[4,5-c]pyridine        (GPC-13)

Part B

Methodology for Determination of Antiviral and Cytostatic Activity

Cells and Viruses

Madin-Darbey Bovine Kidney (MDBK) cells were maintained in Dulbecco'smodified Eagle medium (DMEM) supplemented with BVDV-free 5% fetal calfserum (DMEME-FCS) at 37° C. in a humidified, 5% CO₂ atmosphere. BVDV-1(strain PE515) was used to assess the antiviral activity in MDBK cells.Vero cells were maintained in the same way as MDBK cells. Vero cellswere infected with Coxsackie B3 virus (strain Nancy).

Determination of Cytostatic Effect on MDBK Cells

The effect of the drugs on exponentially growing MDBK cells was assessedas follows. Cells were seeded at a density of 5000 cell/well in 96 wellplates in MEM medium (Gibco) supplemented with 10% fetal calf serum, 2mM L-glutamine (Life Technologies) and bicarbonate (Life Technologies).Cells were cultured for 24 hr after which serial dilutions of the testcompounds were added. Cultures were then again further incubated for 3days after which the effect on cell growth was quantified by means ofthe MTS method (Promega). The concentration that results in 50%inhibition of cell growth is defined as the 50% cytostatic concentration(CC₅₀)

Anti-BVDV assay

Ninety-six-well cell culture plates were seeded with MDBK cells inDMEM-FCS so that cells reached 24 hr later confluency. Then medium wasremoved and serial 5-fold dilutions of the test compounds were added ina total volume of 100 ul, after which the virus inoculum (100 ul) wasadded to each well. The virus inoculum used resulted in a greater than90% destruction of the cell monolayer after 5 days incubation at 37° C.Uninfected cells and cells receiving virus without compound wereincluded in each assay plate. After 5 days, medium was removed and 90 μlof DMEM-FCS and 10 ul of MTS/PMS solution (Promega) was added to eachwell. Following a 2 hr incubation period at 37° C. the optical densityof the wells was read at 498 nm in a microplate reader. The 50%effective concentration (EC₅₀) value was defined as the concentration ofcompound that protects 50% of the cell monolayer from virus-inducedcytopathic effect.

Anti-HCV Assay/Replicon Assay

Huh-5-2 cells [a cell line with a persistent HCV repliconI3891uc-ubi-neo/NS3-3′/5.1; replicon with fireflyluciferase-ubiquitin-neomycin phosphotransferase fusion protein andEMCV-IRES driven NS3-5B HCV polyprotein] was cultured in RPMI medium(Gibco) supplemented with 10% fetal calf serum, 2 mM L-glutamine (LifeTechnologies), 1× non-essential amino acids (Life Technologies); 100IU/ml penicillin and 100 ug/ml streptomycin and 250 ug/ml G418(Geneticin, Life Technologies). Cells were seeded at a densitiy of 7000cells per well in 96 well View Plate™ (Packard) in medium containing thesame components as described above, except for G418. Cells were allowedto adhere and proliferate for 24 hr. At that time, culture medium wasremoved and serial dilutions of the test compounds were added in culturemedium lacking G418. Interferon alfa 2a (500 IU) was included as apositive control. Plates were further incubated at 37° C. and 5% CO₂ for72 hours. Replication of the HCV replicon in Huh-5 cells results inluciferase activity in the cells. Luciferase activity is measured byadding 50 μl of 1× Glo-lysis buffer (Promega) for 15 minutes followed by50 ul of the Steady-Glo Luciferase assay reagent (Promega). Luciferaseactivity is measured with a luminometer and the signal in eachindividual well is expressed as a percentage of the untreated cultures.Parallel cultures of Huh-5-2 cells, seeded at a density of 7000cells/well of classical 96-well cell culture plates (Becton-Dickinson)are treated in a similar fashion except that no Glo-lysis buffer orSteady-Glo Luciferase reagent is added. Instead the density of theculture is measured by means of the MTS method (Promega).

Quantitative Analysis of HCV RNA by Tagman Real-Time RT-PCR

Replicon cells were plated at 7.5×10³ cells per well in a 96-well plateplates at 37° C. and 5% CO₂ in Dulbecco's modified essential mediumcontaining 10% fetal calf serum, 1% nonessential amino acids and 1 mg/mlGeneticin. After allowing 24 h for cell attachment, different dilutionsof compound were added to the cultures. Plates were incubated for 5days, at which time RNA was extracted using the Qiamp Rneazyi Kit(Qiagen, Hilden, Germany). A 50 μL PCR reaction contained TaqMan EZbuffer (50 mmol/L Bicine, 115 mmol/L potassium acetate, 0.01 mmol/LEDTA, 60 nmol/L 6-carboxy-X-rhodamine, and 8% glycerol, pH 8.2; PerkinElmer Corp./Applied Biosystems), 300 μmol/L deoxyadenosine triphosphate,300 μmol/L deoxyguanosine triphosphate, 300 μmol/L deoxycytidinetriphosphate, 600 μmol/L deoxyuridine triphosphate, 200 μmol/L forwardprimer [5′-ccg gcT Acc Tgc ccA TTc], 200 μmol/L reverse primer [ccA GaTcAT ccT gAT cgA cAA G], 100 μmol/L TaqMan probe [6-FAM-AcA Tcg cAT cgAgcg Agc Acg TAc-TAMRA], 3 mmol/L manganese acetate, 0.5 U AmpEraseuracil-N-glycosylase, 7.5 U rTth DNA polymerase, and 10 μl of RNAelution. After initial activation of uracil-N-glycosylase at 50° C. for2 minutes, RT was performed at 60° C. for 30 minutes, followed byinactivation of uracil-N-glycosylase at 95° C. for 5 minutes. SubsequentPCR amplification consisted of 40 cycles of denaturation at 94° C. for20 seconds and annealing and extension at 62° C. for 1 minute in an ABI7700 sequence detector. For each PCR run, negative template and positivetemplate samples were used. The cycle threshold value (Ct-value) isdefined as the number of PCR cycles for which the signal exceeds thebaseline, which defines a positive value. The sample was considered tobe positive if the Ct-value was <50. Results are expressed as genomicequivalents (GE).

Anti-Coxsackie Virus Assay

Ninety-six-well cell culture plates were seeded with Vero cells in DMEMmedium containing 10 fetal calf serum (FCS) so that cells reachedconfluency 24-48 hr later. Medium was then removed and serial 5-folddilutions of the test compounds were added in a total volume of 100 ul,after which the virus inoculum (100 μl) was added to each well. Thevirus inoculum used resulted in a 90-100% destruction of the cellmonolayer after 5 days incubation at 37° C. Uninfected cells and cellsreceiving virus without compound were included in each assay plate.After 5 days, the medium was removed and 90 μl of DMEM-FCS and 10 μl ofMTS/PMS solution (Promega) was added to each well. Following a 2 hrincubation period at 37° C., the optical density of the wells was readat 498 nm in a microplate reader. The 50% effective concentration (EC50)value was defined as the concentration of compound that protects 50% ofthe cell monolayer from virus-induced cytopathic effect

Example 66 Determination of the Mechanism of Action of the Compounds

Generation of Drug-Resistant Virus and Determination of the Pheno- andGenotype of the Resistant Virus

Wild type BVDV (strain NADL) was twice plaque purified on MDBK cells.The entire coding region of the genome of this virus was sequenced. Thisplaque purified and sequenced virus was then cultured in the presence ofincreasing drug concentrations of compound (GPJN22). Following 12passages, the virus was at least 25 fold resistant to compound GPJN22.The resistant virus preparation was again plaque purified. The entirecoding region of the genome of this virus was sequenced. A mutationF224S in the RNA dependent RNA polymerase gene of the virus was detectedin 4 out of 4 clones of this virus; no other mutations were detected inthe resistant viruses. The GPJN22-resistant virus was cross-resistantwith VP32947 (see Table 8). VP32947 is an earlier reported selectiveinhibitor of BVDV replication [Baginski S G et al., Proc Natl Acad Sci US A. 2000 Jul 5;97(14):7981-6]. In VP32947-resistant BVDV, a similarmutation was identified as being responsible for the drug-resistance. Toconfirm that the F224S mutation is indeed responsible for the resistantphenotype, the mutation was reintroduced by site-directed mutagenesis inan full-length infectious clone of the BVDV (strain NADL) [Vassilev etal., J Virol. 1997 Jan;71(1):471-8.]. The recombinant virus thusgenerated exhibited the same drug-resistance profile as the F224S mutantvirus that was generated following culturing in increasing drugconcentrations.

Example 67 Anti-BVDV (Strain PE515) Activity in MDBK Cells

The results of the testing of the compound of the invention in theanti-BVDV assay described above are provided in Table 9. TABLE 9 EC₅₀CC₅₀ Compound example (μg/ml) (μg/ml) SI GPJN-1 4 0.240 >83.3 >345GPJN-3 5 0.060 60 1003 GPJN-4 6 0.040 46 1144 GPJN-7 9 0.042 22 525GPJN-8 10 0.086 51 592 GPJN-9 11 0.049 GPJN-9 xHCl 25 0.016 GPJN-11 120.032 36 1135 GPJN-12 13 0.059 56 949 GPJN-13 14 0.043 45 1058 GPJN-14 80.070 40 573 GPJN-15 17 0.009 29 3079 GPJN-16 21 0.246 8.1 33 GPJN-17 180.097 50 517 GPJN-18 19 0.019 55 2933 GPJN-19 20 0.013 40 3012 GPJN-2015 0.165 28 169 GPJN-21 16 0.022 22 1020 GPJN-22 22 0.029 13 450 GPJN-2323 0.014 46 3230 GPJN-24 24 0.040 21 519 GPJN-25 26 0.009 36 4138GPJN-26 27 0.041 >100 >2439 GPJN-27 28 0.945 >46 >48 GPJN-28 290.325 >75 >230 GPJN-31 32 0.455 >100 >222 GPJN-32 35 0.027 20 741GPJN-33 36 0.200 70 350 GPJN-34 33 0.865 >100 >116 GPJN-35 340.365 >100 >273 GPJN-36 37 0.019 24 1297 GPJN-37 38 0.161 22 137 GPJN-3839 0.235 50 213 GPJN-39 40 0.245 >100 >408 GPJN-40 41 0.250 >100 >400GPJN-41 42 0.580 >100 >172 GPJN-48 43 0.351 >100 >285 GPJN-49 49 0.18062 344 GPJN-50 0.021 >100 >4760 GPJN-53 50 0.033 66 2028 GPJN-54 440.100 35 349 GPJN-55 45 0.060 >100 >1666 GPJN-58 47 0.052 8.1 156GPJN-60 0.015 >77 5133 GPJN-62 52 0.120 9.4 78 GPJN-63 53 0.0042 4.31023 GPJN-64 0.026 >100 >3846 GPJN-65 0.01 >100 >10.000 GPJN-68 0.026 17653 GPJN-73 0.017 >100 >5882 GPJN-75 0.018 31.7 1761 GPJN-790.083 >100 >1204 GPJN-80 0.18 >100 >555 GPC-10 0.064 4 62.5 GPC-110.56 >100 >178 GPC-13 0.067 >100 >1492 GPRTI-8 3 0.137 >79 >576VP32947** 0.003 47 >16785**Baginsky et al., Proc Natl Acad Sci U S A Jul 5, 2000; 97(14): 7981-6EC₅₀: effective concentration required to reduce virus inducedcytopathic effect in MDBK cells by 50%.IC₅₀: inhibitory concentration required to reduce the growth ofexponentially growing MDBK cells by 50%SI: IC₅₀/EC₅₀.Data are mean values for 2-5 independent determinations

Example 68 Anti-BVDV Activity of Compounds GPJN-100 to GPJN-115

TABLE 10 Compound example EC₅₀ (μg/ml) MTC (μg/ml) SI GPJN-100 0.088 20227 GPJN-103 65 0.061 20 328 GPJN-104 0.27 20 74 GPJN-105 0.021 100 4762GPJN-107 0.088 100 1136 GPJN-108 0.061 20 328 GPJN-109 0.27 20 74GPJN-110 57 0.021 4 190 GPJN-112 58 0.0049 20 4082 GPJN-113 59 0.0031 206452 GPJN-114 60 0.021 20 952 GPJN-115 61 0.24 4 17EC₅₀: effective concentration required to reduce virus inducedcytopathic effect in MDBK cells by 50%.MTC: mean toxic concentration, concentration required to reduce thegrowth of exponentially growing MDBK cells by 50%SI: MTC/EC₅₀.

Example 69 Effect of Compounds in HCV-Huh-5-2 Replicon Cells

TABLE 11 Compound EC50 CC50 SI GPJN-16 1 3  3 GPJN-52 0.2 24 118 GPJN-580.13 2  15 GPJN-62 <0.62 6 >10¹⁰ GPJN-83 <0.62 8 >12 GPJN-87 <0.6220 >32 GPJN-96 1 4  3 GPJN-110 0.21 5.9  28 GPJN-112 0.29 >17 >58¹⁵GPJN-113 0.17 14  82 GPJN-114 0.12 6.15  50EC50: concentration required to inhibit luciferase activity in thereplicon system by 50%.CC50: concentration required to inhibit the proliferation ofexponentially growing Huh-5-2 cells by 50%.

Example 70 Effect of GPJN-52 and GPJN-58 on Replicon (RNA) Synthesis inHuh-5-2 Cells.

TABLE 12 CT Delta CT    5 ug/ml GPJN 52 31.14 2.28    1 ug/ml GPJN 5230.23 1.37   0.2 ug/ml GPJN52 29.25 0.39  0.04 ug/ml GPJN52 29.11 0.25 0.01 ug/ml GPJN52 29.00 0.14    1 ug/ml GPJN-58 32.86 4   0.2 ug/mlGPJN-58 30.00 1.14  0.04 ug/ml GPJN-58 29.89 1.03  0.008 ug/ml GPJN-5829.75 0.89 0.0016 u/ml GPJN-58 28.91 0.05 untreated 28.86 ± 0.04Effect of the antivirals on the synthesis of the HCV replicon asdetermined by means of real-time quantitative RT-PCR. A higher Delta CTvalue indicates a more profound inhibition of viral RNA synthesis.

Example 71 Antioxsackie B3 Activity in Vero Cells

TABLE 13 TC₅₀ Compound example EC₅₀ (μg/ml) (μg/ml) SI GPJN-5 6.0 >10016.6 GPJN-32 35 6.5 69 15.4 GPJN-40 41 8.95 >100 11.2 GPJN-50 8.47 >10011.8 GPJN-60 6.1 >100 16.4 GPJN-64 12 >42 3.5 GPC-10 1.81 59 32.59GPC-11 4.76 >100 21.0 GPC-12 3.6 >100 27.7 GPRTI-8 3 12.2 >100 8.48EC₅₀: effective concentration required to reduce virus (CBV-3 Nancystrain)-induced cytopathic effect in Vero cells by 50%.IC₅₀: effective concentration required to reduce the metabolism ofconfluent Vera cells by 50% as determined by the MTS method.SI: IC₅₀/EC₅₀.Data are mean values for two or more independent determinations

1. Use of a imidazo[4,5-c]pyridine derivative of the formula (Z), orpharmaceutically acceptable salts thereof for the preparation of amedicament for the treatment or prevention of viral infections,

wherein: the dotted lines represent an optional double bond, providedthat no two double bonds are adjacent to one another, and that thedotted lines represent at least 3, optionally 4 double bonds; R¹ isselected from hydrogen; aryl unsubstituted or substituted with one ormore R⁶, heterocyclic ring unsubstituted or substituted with one or moreR, C₃₋₁₀ cycloalkyl unsubstituted or substituted with one or more R⁶ andC₄₋₁₀ cycloalkenyl unsubstituted or substituted with one or more R⁶; Yis selected from the group consisting of a single bond, O; S(O)_(m);NR¹¹; and a divalent, saturated or unsaturated, substituted orunsubstituted C₁-C₁₀ hydrocarbon group optionally including one or moreheteroatoms in the main chain, said heteroatoms being selected from thegroups consisting of O, S, and N; such as C₁₋₆ alkylene, C₂₋₆alkenylene, C₂₋₆ alkynylene, —O(C₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—,—S—(CH₂)₁₋₄—, —(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—,—(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄— and C₃₋₁₀ cycloalkylidene; each R² and R⁴ isindependently selected from the group consisting of hydrogen C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ is alkynyl; C₁₋₁₈ alkoxy, C₁₋₁₈ alkylthio;halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH;aryl; aryloxy; arylthio, arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀cycloalkyl; C₃₋₁₀ cycloalkoxy; C₃₋₁₀ cycloalkylthio; C₃₋₁₀ cycloalkenyl;C₃₋₁₀ cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring; or, when one of R²⁵ or R²⁶ is different fromhydrogen, either R² or R⁴ is selected from (═O), (═S), and (═N²⁷); X isselected from the group consisting of a divalent, saturated orunsaturated, substituted or unsubstituted C₁-C₁₀ hydrocarbon groupoptionally including one or more heteroatoms in the main chain (providedthat the heteroatom is not linked to N of the nucleus), said heteroatomsbeing selected from the group consisting of O, S, and N; such as C₁₋₆alkylene, (for example —CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—,—CH₂—CH₂—CH₂—CH₂), —(CH₂)₂₋₄—O—(CH₂)₂₋₄—, —(CH₂)₂₋₄—S—(CH₂)₂₋₄—,—(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene (suchas —CH═CH—CH₂—), C₂₋₆ alkylene; m is any integer from 0 to 2; R³ isselected from the group consisting of aryl; aryloxy, arylthio;aryl-N¹⁰—; 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring; and each of said aryl, aryloxy, arylthio,aryl-NR¹⁰—, 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring is optionally substituted with one or more R¹⁷;C₃₋₁₀ cycloalkyl, oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenylwith the proviso that the double bond cannot be adjacent to a nitrogen;H with the proviso that if X is an alkylene, an arylene or analkarylene, then X comprises at least 5 carbon atoms; R⁵ isindependently selected from the group consisting of hydrogen; C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy, C₁₋₁₈ alkylthiohalogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH;aryl; aryloxy, arylthio; arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀cycloalkyl; C₃₋₁₀ cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀cycloalkenyl; C₃₋₁₀ cycloalkynyl; 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring; each R⁶ and R¹⁷ isindependently selected from the group consisting of hydrogen; C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkyl; C₁₋₁₈ alkoxy, C₁₋₁₈ alkylthio; C₃₋₁₀cycloalkyl, C₃₋₁₀ cycloalkenyl or C₃₋₁₀ cycloalkyl; halogen; OH; CN;NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R¹⁸; C(═S)R¹⁸; SH; aryl; aryl),arylthio; arylalkyl; arylalkyloxy (optionally a oxybenzyl);arylalkylthio (optionally a benzylthio); 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl; and eachof said aryl, aryloxy, arylthio, arylalkyl, arylalkyloxy (optionally aoxybenzyl), arylalkylthio (optionally a benzylthio), 5 or 6 memberedheterocyclic, oxyheterocyclic or thioheterocyclic ring, C₁₋₁₈hydroxyalkyl is optionally substituted with 1 or more R¹⁹; each R⁷ andR⁸ is independently selected from the group consisting of H; C₁₋₁₈alkyl; C₁₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6membered heterocyclic ring; C(═O)R¹²; C(═S)R¹²; an amino acid residuelinked through a carboxyl group thereof; alternatively, R⁷ and R⁸,together with the nitrogen to which they are attached, combine to form a5-6 membered heterocyclic ring; each R⁹ and R¹⁸ is independentlyselected from the group consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl;C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl anamino acid residue linked through an amino group thereof; each R¹⁰ andR¹¹ is independently selected from the group the group consisting of H;C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl;C(═O)R¹²; 5-6 membered heterocyclin ring; an amino acid residue linkedthrough a carboxyl group thereof; R¹² is independently selected from thegroup consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid residue linked throughamino group thereof; each R¹³ and R¹⁴ is independently selected from thegroup consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═S)R¹²; an amino acidresidue linked through a carboxyl group thereof; each R¹⁵ and R¹⁶ isindependently selected from the group consisting of H; C₁₋₁₈ alkyl;C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cyclosyl; C₄₋₁₀ cycloalkenyl;an amino acid residue linked through a carboxyl group thereof. R¹⁹ isindependently selected from the group consisting of H; C₁₋₁₈ alkyl,preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy,preferably C₁₋₆ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl; C₄₋₁₀cycloalkenyl; C₄₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR²⁰R²¹; OCF₃;haloalkyl; C(═O)R²²; C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆alkyl); aryl; aryloxy; arylthio; arylalkyl; and each of said aryl,aryloxy, arylthio, arylalkyl substituted with 1 or more halogens,particularly a phenyl substituted with 1-2 halogens; hydroxyalkyl; 5 or6 membered heterocyclic, oxyheterocyclic or thioheterocyclic ring eachunsubstituted or substituted with 1 or more halogens; each R²⁰ and R²¹is independently selected from the group consisting of H; C₁₋₁₈ alkyl,preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹², C(═S)R¹²; R²² is independentlyselected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴;aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; each R²³ and R²⁴ isindependently selected from the group the group consisting of H; C₁₋₁₈alkyl, preferably C₂₋₃ alkyl, wherein C₂₋₃ alkyl taken together with Nof R²² can form a saturated heterocycle, which heterocycle is optionallysubstituted with OH or aryl or an amino acid residue; each R²⁵ or R²⁶,are absent or selected from the group consisting of of H, C₁₋₁₈ alkyl,preferably C₁₋₄ alkyl; C₃₋₁₀ cycloalkyl, such as C₅₋₁₀ bicycloalkyl;C₃₋₁₀ cycloalkenyl; (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl; aryl, such as phenyl;5 or 6 membered heterocyclic ring, such as pyridyl; alkylaryl, such asbenzyl; and each of said C₁₋₁₈ alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀cycloalkyl, C₃₋₁₀ cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl C₅₋₁₀bicycloalkyl, adamantyl, phenyl, pyridyl and benzyl is optionallysubstituted with 1-4 of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OH,oxybenzyl, and OH; and heterocyclic ring having 3 to 7 carbon atoms,preferably a saturated heterocyclic ring wherein the heteroatoms are S,S(O), or S(O)₂ separated from the imidazopyridyl ring nitrogen atom byat least 2 heterocyclic ring carbon atoms. Provided that either R²⁵ orR²⁶ is hydrogen. Typically R²⁵ or R²⁶ is cyclopentyl or cyclohexyl;provided that if the compound is substituted R²⁵ or R²⁶, either R² or R⁴is selected from (═O), (═S), and (═NR²⁷); and R²⁷ is selected from thegroup consisting of H, C₁₋₁₈ alkyl, C₃₋₁₀ cycloalkyl, (C₃₋₁₀cycloalkyl)-C₁₋₆ alkyl; aryl; arylalkyl, such as benzyl.
 2. The useaccording to claim 1, wherein said viral infection is an infection of avirus belonging to the family of Flaviviridae.
 3. The use according toclaim 1, wherein said viral infection is an infection of a hepatitis-Cvirus.
 4. The use according to claim 1, wherein said viral infection isan infection of a virus belonging to the family of the Picornaviridae.5. The use according to claim 1, wherein said viral infection is aninfection of a Coxsackie virus.
 6. The use of claim 1, wherein saidcompound is selected from the group consisting of:5-[(4-Bromophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-(2-pyridinyl)-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-(1-naphthalenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-[(phenylthio)methyl]-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-[3-(trifluoromethyl)phenyl]-5H-imidazo[4,5-c]pyridine5-[(1,1′-Biphenyl]-4-ylmethyl)-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Chlorophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine2(2-Fluorophenyl)-5-[(4-iodophenyl)methyl)-5H-imidazo[4,5-c]pyridine5-[[4-(1,1-Dimethylethyl)phenyl]methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine7. An imidazo[4,5-c]pyridine compound according to formula A:

or an enantiomer or a solvate, or a pharmaceutically acceptable saltthereof, wherein: the dotted lines represent an optional double bond,provided that no two double bonds are adjacent to one another, and thatthe dotted lines represent at least 3, optionally 4 double bonds; R¹ isselected from hydrogen; aryl unsubstituted or substituted with one ormore R⁶, heterocyclic ring unsubstituted or substituted with one or moreR⁶, C₃₋₁₀ cycloalkyl unsubstituted or substituted with one or more R⁶and C₄₋₁₀ cycloalkenyl unsubsituted or substituted with one or more R⁶ Yis selected from the group consisting of a single bond, O; S(O)_(m),NR¹¹; and a divalent, saturated or unsaturated, substituted orunsubstituted C₁-C₁₀ hydrocarbon group optionally including one or moreheteroatoms in the main chain, said heteroatoms being selected from thegroups consisting of O, S, and N; such as C₁₋₆ alkylene, C₂₋₆alkenylene, C₂₋₆ alkylene, —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—,—S—(CH₂)₁₋₅—, —(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₄—,—(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄— and C₃₋₁₀ cycloalkylidene; each R² and R⁴ isindependently selected from the group consisting of hydrogen C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio;halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH;aryl; aryloxy; arylthio; aIylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀cycloalkyl; C₃₋₁₀ cycloalkyloxy; C₃₋₁₀ cycloalkylthio; C₃₋₁₀cycloalkenyl; C₃₋₁₀ cycloalkyl; 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring; or, wherein of R²⁵ or R²⁶ isdifferent from hydrogen, either R² or R⁴ is selected from (═O), (═S),and (═NR²⁷); X is selected from the group consisting of a divalent,saturated or unsaturated, substituted or unsubstituted C₁₋₁₀ hydrocarbongroup optionally including one or more heteroatoms in the main chain(provided that the heteroatom is not linked to N of the nucleus), saidheteroatoms being selected from the group consisting of O, S, and N;such as C₁₋₆ alkylene, (for example —CH₂—, —CH(CH₃)—, —CH₂—CH₂—,—CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂), —(CH₂)₂₋₄—O—(CH₂)₂₋₄,—(CH₂)₂₋₄—S—(CH₂)₂₋₄—, —(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene,C₂₋₆ alkenylene (such as —CH═CH—CH₂—), C₂₋₆ alkynylene; m is any integerfrom 0 to 2; R³ is selected from the group consisting of aryl; aryloxy;arylthio; aryl-NR¹⁰—; 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring,; and each of said aryl, aryloxy, arylthio,aryl-NR¹⁰—, 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring is optionally substituted with one or more R¹⁷;C₃₋₁₀ cycloalkyl, oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenylwith the proviso that the double bond cannot be adjacent to a nitrogen;H with the proviso that if X is an alkylene, an alkenylene or analkynylene, then X comprises at least 5 carbon atoms; R⁵ isindependently selected from the group consisting of hydrogen; C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio;halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH;aryl; aryloxy; arylthio; arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀cycloalkyl; C₃₋₁₀ cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀cycloalkenyl; C₃₋₁₀ cycloalkynyl; 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring; each R⁶ and R¹⁷ isindependently selected from the group consisting of hydrogen; C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio;C₃₋₁₀ cycloalkyl, C₃₋₁₀ cycloalkenyl or C₃₋₁₀ cycloalkyl; halogen; OH;CN; NO; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R¹⁸; C(═S)R¹⁸; SH; aryl; aryloxy,arylthio; arylalkyl; arylalkyloxy (optionally a oxybenzyl);arylalkylthio (optionally a benzylthio); 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈ hydroxyalkyl; and eachof said aryl, aryloxy, arylthio, arylalkyl, arylalkyloxy (optionally aoxybenzyl), arylalkylthio (optionally a benzylthio), 5 or 6 memberedheterocyclic, oxyheterocyclic or thioheterocyclic ring, C₁₋₁₈hydroxyalkyl is optionally substituted with 1 or more R¹⁹; each R⁷ andR⁸ is independently selected from the group consisting of H; C₁₋₁₈alkyl; C₁₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6membered heterocyclic ring; C(═O)R¹²; C(═S)R¹² ; an amino acid residuelinked through a carboxyl group thereof; alternatively, R⁷ and R⁸,together with the nitrogen to which they are attached, combine to form a5-6 membered heterocyclic ring; each R⁹ and R¹⁸ is independentlyselected from the group consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkyl;C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy, NR¹⁵R¹⁶; aryl anamino acid residue linked through an amino group thereof; each R¹⁰ andR¹¹ is independently selected from the group the group consisting of H;C₁₋₁₈ alkyl C₁₋₁₈ alkenyl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl;C(═O)R¹²; 5-6 membered heterocyclin ring; an amino acid residue linkedthrough a carboxyl group thereof; R¹² is independently selected from thegroup consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid residue linked through anamino group thereof; each R¹³ and R¹⁴ is independently selected from thegroup consisting of H; C₁₋₁₈ alkyl; C₂₋₈ alkenyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═SR)R¹²; an amino acidresidue linked through a carboxyl group thereof; each R¹⁵ and R¹⁸ isindependently selected from the group consisting of H; C₁₋₁₈ alkyl;C₂₋₁₈ alkenyl; C₂₋₁₈ is alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀cycloalkenyl; an amino acid residue linked through a carboxyl groupthereof. R¹¹ is independently selected from the group consisting of H;C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkyl; C₁₋₁₈alkoxy, preferably C₁₋₆ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl; C₄₋₁₀cycloalkynyl; C₄₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR²⁰R²¹, OCF₃;haloalkyl; C(═O)R²²; C(═S)R²²; SH C(═)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆alkyl); aryl; aryloxy; arylthio; arylalkyl; and each of said aryl,aryloxy, arylthio, arylalkyl substituted with 1 or more halogens,particularly a phenyl substituted with 1-2 halogens; hydroxyalkyl; 5 or6 membered heterocyclic, oxyheterocyclic or thioheterocyclic ring eachunsubstituted or substituted with 1 or more halogens; each R²⁰ and R²¹is independently selected from the group consisting of H; C₁₋₁₈ alkyl,preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹², C(═S)R¹²; R²² is independentlyselected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴;aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; each R²³ and R²⁴ isindependently selected from the group the group consisting of H; C₁₋₈alkyl, preferably C₂₋₃ alkyl, wherein C₂₋₃ alkyl taken together with Nof R²² can form a saturated heterocycle, which heterocycle is optionallysubstituted with OH or aryl or an amino acid residue; each R²⁵ or R²⁶,are absent or selected from the group consisting of of H, C₁₋₁₈ alkyl,preferably C₁₋₄ alkyl; C₃₋₁₀ cycloalkyl, such as C₅₋₁₀ bicycloalkyl;C₃₋₁₀ cycloalkenyl; (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl; aryl, such as phenyl;5 or 6 membered heterocyclic ring, such as pyridyl; alkylaryl, such asbenzyl; and each of said C₁₋₁₈ alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀cycloalkyl, C₃₋₁₀ cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl, C₅₋₁₀bicycloalkyl, adamantyl, phenyl, pyridyl and benzyl is optionallysubstituted with 1-4 of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OH,oxybenzyl, and OH; and heterocyclic ring having 3 to 7 carbon atoms,preferably a saturated heterocyclic ring wherein the heteroatoms are S,S(O), or S(O)₂ separated from the imidazopyridyl ring nitrogen atom byat least 2 heterocyclic ring carbon atoms. Provided that either R²⁵ orR²⁶ is hydrogen. Typically R²⁵ or R²⁶ is cyclopentyl or cyclohexyl;provided that if the compound comprises R²⁵ or R²⁶, either R² or R⁴ isselected from (═O), (═S), and (═NR²⁷); and R²⁷ is selected from thegroup consisting of H, C₁₋₁₈ alkyl, C₃₋₁₀ cycloalkyl, (C₃₋₁₀cycloalkyl)C₁₋₆ alkyl; aryl; arylalkyl, such as benzyl; with the provisothat: the substituents X, Y, R¹, R², R³, R⁴, R⁵ are not a cephalosporinor wherein the substitute X, Y, R¹, R², R³, R⁴, R⁵ are not an azabicyclogroup, more particularly not 5-thia-1-aza-bicyclo[4.2.0]oct-2-en-8-one;the compound is not5-(2-piperidin-1-yl-ethyl)-2-(4hydroxyphenyl)-1H-imidazo[4,5c]pyridin-5-iumbromide; the compound is not4-[5-(2-{4-[Bis-(4-fluorophenyl)-methyl]-piperazin-1-yl}-ethyl)-5H-imidazo[4,5-c]pyridin-2-yl]phenol;the compound is not4-[5-(3-{4-Bis-(4-fluorophenyl)-methyl]-piperazin-1-yl}-propyl)-5H-imidazo[4,5-c]pyridin-2-yl]phenol,the compound is not2,6-bis(1,1,-dimethylethyl)-4-[[2-(5H-imidazo-[4,5-c]pyridin-5-yl)ethyl]thio]-phenolhydrate and/or2,6-bis(1,1,-dimethylethyl)-4-[[2-(5H-imidazo-[4,5-c]pyridin-5-yl)propyl]thio]-phenolhydrate the compound is not a compound wherein XR³ has the structure—(CH₂)n-Y′—CO—. N(R₁′)(R₂′) wherein R₁′ and R₂′ are each independentlyselected from hydrogen, straight or branched chain alkyl of 1 to 15carbon atoms; cycloalkyl having 3 to 8 carbon atoms; substitutedcycloalkyl which can be substituted one or more by alkyl of 1 to 6carbon atoms; bicycloalkyl having 3 to 8 carbon atoms in each ring;heterocyclicalkyl having 4 to 8 carbon atoms which can be optionallysubstituted by alkyl of 1 to 6 carbon atoms; heteroaromatic having 5 or6 carbon atoms which can be optionally substituted by alkyl having 1 to6 carbon atoms; phenyl; substituted phenyl which can be substituted oneor more by a group independently selected from alkyl having 1 to 6carbon atoms or halogen; straight or branched alkenyl having 3 to 15carbon atoms with the proviso that the double bond of the alkenyl groupcannot be adjacent to the nitrogen; cycloalkenyl having 5 to 8 carbonatoms with the proviso that the double bond cannot be adjacent to thenitrogen; and R₁′ and R₂′ cannot both be hydrogen; Y′ is phenyl orphenyl substituted once or more than at one or more of the 2, 3, 5 or 6positions of the phenyl ring by substituents independently selected fromthe group consisting of alkoxy having 1 to 6 carbon atoms; halogenwherein the halogen is selected from bromo, fluoro, or chloro; straightor branched chain alkyl having 1 to 6 carbon atoms; substituted straightor branched chain alkyl which can be substituted one or more by halogen;thioalkyl wherein the alkyl has 1 to 6 carbon atoms; alkoxyalkyl whereinthe alkyl groups are each 1 to 6 carbon atoms; hydroxyalkyl wherein thealkyl has 1 to 6 carbon atoms; alkylthioalkyl wherein the alkyl groupsare each 1 to 6 carbon atoms; cyano; mercaptoallyl wherein the alkyl has1 to 6 carbon atoms; hydroxy; amino; alkylamino wherein the alkyl grouphas 1 to 6 carbon atoms; and dialkylamino wherein the alkyl groups areeach 1 to 6 carbon atoms; n is an integer of 1 to 5 the compound is not5-[2-(Biphenyl-4-yloxy)-ethyl]-5H-imidazo[4,5-c]pyridine; the compoundis not 5-[2-(4-Phenoxy-phenoxy)-ethyl]-5H-imidazo[4,5-c]pyridine; thecompound is not[5-(4-Fluorobenzyl)-5H-imidazo[4,5-c]pyridin-2-yl]-methylamine; thecompound is not2,6-bis(1,1,-dimethylethyl)-4-[[3-(5H-imidazo-[4,5-c]pyridin-5-yl)propyl]thio]-phenolhydrate; the compound is not5-[2-(4-Phenylmethyloxy-phenoxy)-ethyl]-5H-imidazo[4,5-c]pyridine; thecompound is not5-[3-(4-Phenoxy-phenoxy)-propyl]-5H-imidazo[4,5-c]pyridine the compoundis not 5-{2-[4-(4-Fluorophenoxy)-phenoxy]-ethyl}-5H-imidazo[4,5]pyridin. the compound is not5-[3-(4-Phenylmethyl-phenoxy)-propyl]-5H-imidazo[4,5-c]pyridine; thecompound is not((5-[4-(Fluorophenyl)methyl]-5-H-imidazo[4,5-c]-pyridine-2-yl)methyl)-carbamaat, methyl ester; the compound is not5-(4-Chlorophenylmethyl)-2-(piperidin-1-ylmethyl)-5H-imidazo[4,5-c]pyridineand its dihydrochloride salt; the compound is not5-(4-Chlorophenylmethyl)-2-(4-methyl-piperzin-1-ylmethyl)-5H-imidazo[4,5]pyridine;the compound is not5-(5-(5-azabenzimidazolyl)methyl)-1-(4-cyanobenzyl)imidazole; thecompound is not5-(5-benzyl-2,3-dihydro-benzofuran-2-ylmethyl)-5H-imidazo[4,5-c]pyridine;the compound is not 5-[2-[4-(phenylmethyl)phenoxy]ethyl]-5H-imidazo[4,5-c]-pyridine hydrate; the compound is not5-[2-[4-(phenylethoxy) phenoxy]ethyl]-5H-imidazo[4,5-c]-pyridine; thecompound is not5-[2-[4-(phenoxyphenoxy)ethyl]-5H-imidazo[4,5-c]-pyridine; the compoundis not 5-[3-[4-(phenoxyphenoxy)propyl]-5H-imidazo[4,5-c]-pyridine; thecompound is not5-[2-[4-(4-fluorophenoxy)phenoxy)ethyl]-5H-imidazo[4,5c]-pyridine; thecompound is not5-[3-[4(phenylmethyl)phenoxypropyl]-5H-imidazo[4,5-c]-pyridine; thecompound is not2,6-bis(1,1,-dimethylethyl)-4-[[3-(5H-imidazo-[4,5-c]pyridin-5-yl)propyl]thio]-phenolhydrate; the compound is not2,6-bis(1,1,-dimethylol)-4-[[2-(5H-imidazo-[4,5-c]pyridin-5-yl)ethyl]thio]-phenolhydrate; the compound is not2,6-bis(1,1-dimethylethyl)-4-[[4-(5H-imidazo-[4,5]pyridin-5-yl)butyl]thio]-phenolhydrate; the compound is not (±)2,6-bis(1,1,-dimethylethyl)-4-[[2-hydroxy-3]-(5h-imidazo-(4,5-c]pyridin-5-yl)butyl]thio]-phenolhydrate;
 8. The compound according to claim 7, wherein:= R¹ is selectedfrom hydrogen; aryl unsubstituted or substituted with one or more R⁶,heterocyclic ring unsubstituted or substituted with one or more R⁶,C₃₋₁₀ cycloalkyl unsubstituted or substituted with one or more R⁶ andC₄₋₁₀ cycloalkenyl unsubstituted or substituted with one or more R⁶; Yis selected from the group consisting of a single bond, O; S(O)_(m);NR¹¹; and a divalent, saturated or unsaturated, substituted orunsubstituted C₁-C₁₀ hydrocarbon group optionally including one or moreheteroatoms in the main chain, said heteroatoms being selected from thegroups consisting of O, S, and N; such as C₁₋₆ alkylene, C₂₋₆alkenylene, C₂₋₆ alkynylene, —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—,—S—(CH₂)₁₋₅—, —(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—,—(CH₂)₁₋₄NR¹¹—(CH₂)₁₋₄— and C₃₋₁₀ cycloalkylidene; each R² and R⁴ isindependently selected from the group consisting of hydrogen C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio;halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH:aryl; aryloxy; arylthio; arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀cycloalkyl; C₃₋₁₀ cycloalkyloxy; C₃₋₁₀ cycloalkylthio; C₃₋₁₀cycloalkenyl; C₃₋₁₀ cycloalkynyl; 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring; X is selected from the groupconsisting of a divalent, saturated or unsaturated substituted orunsubstituted C₁₋C₁₀ hydrocarbon group optionally including one or moreheteroatoms in the main chain (provided that the heteroatom is notlinked to N of the nucleus), said heteroatoms being selected from thegroup consisting of O, S, and N; such as C₁₋₆ alkylene, (for example—CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂CH₂—, —CH₂—CH₂—CH₂—CH₂),—(CH₂)₂₋₄—O—(CH₂)₂₋₄—, —(CH₂)₂₋₄—S—(CH₂)₂₋₄—, —(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—,C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene (such as —CH═CH—CH₂—), C₂₋₆alkynylene; m is any integer from 0 to 2; R³ is selected from the groupconsisting of aryl; aryloxy; arylthio; aryl-NR¹⁰—; 5 or 6 memberedheterocyclic, oxyheterocyclic or thioheterocyclic ring; and each of saidaryl, aryloxy, arylthio, aryl NR¹⁰—, 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring is optionally substituted withone or more R¹⁷; C₃₋₁₀ cycloalkyl, oxycycloalkyl or thiocycloalkyl;C₄₋₁₀ cycloalkenyl with the proviso that the double bond cannot beadjacent to a nitrogen; H with the proviso that if X is an alkylene, analkenylene or an alkynylene, then X comprises at least 5 carbon atoms;R⁵ is independently selected from the group consisting of hydrogen;C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹;C(═S)R⁹; SH; aryl; aryloxy; arylthio; arylalkyl; C₁₋₁₈ hydroxyalkyl;C₃₋₁₀ cycloalkyl; C₃₋₁₀ cycloalkyloxy; C₃₋₁₀ cycloalkylthio C₃₋₁₀cycloalkenyl; C₃₋₁₀ cycloalkynyl; 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring; each R⁶ and R¹⁷ isindependently selected from the group consisting of hydrogen; C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ is alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio;C₃₋₁₀ cycloalkyl, C₃₋₁₀ cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH;CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy,arylthio; arylalkyl; arylalkyloxy (optionally a oxybenzyl);arylalkylthio (optionally a benzylthio); 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring; C₁₋₁₈ hydroxyalkyl; and eachof said aryl, aryloxy, arylthio, arylalkyl, arylalkyloxy (optionally aoxybenzyl), arylalkylthio (optionally a benzylthio), 5 or 6 memberedheterocyclic, oxyheterocyclic or thioheterocyclic ring, C₁₋₁₈hydroxyalkyl is optionally substituted with 1 or more R¹⁹; each R⁷ andR⁸ is independently selected from the group consisting of H; C₁₋₁₈alkyl; C₁₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6membered heterocyclic ring; C(═O)R¹²; C(═S) R¹²; an amino acid residuelinked through a carboxyl group thereof; alternatively, R⁷ and R⁸,together with the nitrogen to which they are attached, combine to form a5-6 membered heterocyclic ring; each R⁹ and R¹⁸ is independentlyselected from the group consisting of H; OH; C₁₋₁₈ is alkyl; C₂₋₁₈alkenyl; C₃₋₁₀ cycloalkenyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶;aryl an amino acid residue linked through an amino group thereof; eachR¹⁰ and R¹¹ is independently selected from the group the groupconsisting of H; C₁₋₁₈ alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀ cycloalkyl; C₄₋₁₀cycloalkenyl; aryl; C(═O)R¹²; 5-6 membered heterocyclin ring; an aminoacid residue linked through a carboxyl group thereof; R¹² isindependently selected from the group consisting of H; C₁₋₁₈ alkyl;C₂₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acidresidue linked through an amino group thereof; each R¹³ and R¹⁴ isindependently selected from the group consisting of H; C₁₋₁₈ alkyl;C₂₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²;C(═S)R¹²; an amino acid residue linked through a carboxyl group thereof;each R¹⁵ and R¹⁶ is independently selected from the group consisting ofH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl;C₄₋₁₀ cycloalkenyl; an amino acid residue linked through a carboxylgroup thereof; R¹⁹ is independently selected from the group consistingof H; C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₀ alkenyl; C₂₋₁₈ alkynyl;C₁₋₁₈ alkoxy, preferably C₁₋₆ alkoxy C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl;C₄₋₁₀ cycloalkenyl; C₄₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR²⁰R²¹;OCF₃; haloalkyl; C(═O)R²²; C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl),N(H)S(O)(O)(C₁₋₆ alkyl); aryl; aryloxy; arylthio; arylalkyl; and each ofsaid aryl, aryloxy, arylthio, arylalkyl substituted with 1 or morehalogens, particularly a phenyl substituted with 1-2 halogens;hydroxyalkyl; 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring each unsubstituted or substituted with 1 or morehalogens; each R²⁰ and R²¹ is independently selected from the groupconsisting of H, C₁₋₁₈ alkyl, preferably C₁₋₆alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹², C(═S)R¹²;R²² is independently selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl;C₁₋₁₈ alkoxy; NR²³R²⁴; aryl: C₃₋₁₀ cycloalkyl,; C₄₋₁₀ cycloalkenyl; eachR²³ and R²⁴ is independently selected from the group the groupconsisting of H; C₁₋₁₈ alkyl, preferably C₂₋₃ alkyl, wherein C₂₋₃ alkyltaken together with of R²² can form a saturated heterocycle, whichheterocycle is optionally substituted with OH or aryl or an amino acidresidue; R²⁵ and R²⁶ are hydrogen.
 9. The compound according to claim 7or 8 wherein YR¹ is not hydrogen, an unsubstituted C₃₋₁₀ cycloalkyl, ora C₁₋₆ alkyl.
 10. The compounds according to any one of claims 7 to 9,wherein Y R¹ is not phenyl para substituted with OH.
 11. The compoundsaccording to any of claims 7 to 10 wherein YR¹ is fluorophenyl.
 12. Thecompound according to any one of claims 7 to 10, wherein R¹ is anaphtenyl.
 13. The compound according to any one of claims 7 to 12,wherein R³ is selected from an aryl unsubstituted or substituted with1-3R⁶, wherein at least one R⁶ is a halogen or a C₁₋₆ alkyl
 14. Thecompound according to claim 7, wherein either R² or R⁴ is O and eitherR²⁵ or R²⁶ is cyclopentyl or cyclohexyl.
 15. The compound according toclaim 7, selected from the group consisting of:2-(2,6-Difluorophenyl)-5-[(2,6-difluorophenyl)methyl]-5H-imidazo[4,5-c]pyridine5-Benzyl-2-(2,6-difluorophenyl)-5H-imidazo[4,5c-]pyridine5-[(2,6-Difluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-Benzyl-2-phenyl-5H-imidazo[4,5-c]pyridine2-Phenyl-5-(3-phenylpropyl)-5H-imidazo[4,5-c]pyridine5-[(2-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(3-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(4-Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(2-Metoxyphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(3-Methoxyphenyl)methyl]-2-phenyl-5H-imidazo[4,5c]pyridine5-[(4Methoxyphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(4-Methylphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(2-Fluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(3-Fluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(4-Fluorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(2-Methylphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(3-Methylphenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine4-[(2-Phenyl-5H-imidazo[4,5-c]pyridin-5-yl)methyl]-benzonitrile2-Phenyl-5-[[4-(trifluoromethyl)phenyl]methyl]-5H-imidazo[4,5-c]pyridine5-[(4Chlorophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridinehydrochloride5-[(5-Chloro-2-thienyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine5-(2-Naphthalenylmethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine2-Phenyl-5-(4-phenylbutyl)-5H-imidazo[4,5-c]pyridine5-([1,1′-Biphenyl]-4-ylmethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine2-Phenyl-5-(1-phenylethyl)-5H-imidazo[4,5]pyridine5-(1-Naphthaleylmethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine2-(2,6-Difluorophenyl)-5-[(2,4-difluorophenyl)methyl]-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5c]pyridine5-[(4-Bromophenyl)methyl]-2-(2-chlorophenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl-2-(3-chlorophenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-(4-chlorophenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-(2-pyridinyl)-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-(2-thienyl)-5H-imidazo[4,5-c]pyridine5-[(Bromophenyl)methyl]-2-(1-naphthalenyl)-5H-imidazo[4,5c]pyridine5-[((Bromophenyl)methyl]-2-(2-naphthalenyl)-5H-imidazo[4,5c]pyridine5-[(4-Iodophenyl)methyl)-2-phenyl-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-(3-fluorophenyl)-5H-imidazo[4,5c]pyridine5-[(4-Bromophenyl)methyl]-2-(3-methylphenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-(3-methoxyphenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-(3-bromophenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Chlorophenyl)methyl]-2-(3-bromophenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Chlorophenyl)methyl]-2-(3-chlorophenyl)-5H-imidazo[4,5-c]pyridine;5-(2-Phenoxy-ethyl)-2-phenyl-5H-imidazo[4,5-c]pyridine5-(3-Phenyl-prop-2-en-1-yl)-2-phenyl-5H-imidazo[4,5-c]pyridine2-(3-Bromophenyl)-5-[(4-iodophenyl)methyl]-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-[(phenylthio)methyl]-5H-imidazo[4,5-c]pyridine5-[(4-Bromophenyl)methyl]-2-[3-(trifluoromethyl)phenyl]-5H-imidazo[4,5-c]pyridine5-([1,1′-Biphenyl]-4-ylmethyl)-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine5-[(4-Chlorophenyl)methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine2-(2-Fluorophenyl)-5-[(4-iodophenyl)methyl]-5H-imidazo[4,5-c]pyridine5-[[4-(1,1-Dimethylethyl)phenyl]methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine16. A composition for separate, combined or sequential use in thetreatment or prophylaxis of anti-viral infections, comprising: a) one ormore compounds according to claim 7, and, b) one or more compoundseffective in the treatment or prophylaxis of viral infections, includingFlaviviral or Picornaviral endue inhibitors, in proportions such as toprovide a synergistic effect in the said treatment of prophylaxis. 17.The composition according to claim 16, wherein said one or morecompounds effective in the treatment or prophylaxis of viral infectionsare interferon alpha or ribavirin.
 18. The use of the compounds of anyone of claims 7 to 15 for the preparation of a medicament for thetreatment of viral infections.
 19. A method for preparing the compoundsof claim 7 comprising essentially the steps of a) reacting a(substituted) 3,4-diaminopyridine (A) is reacted with B (Y—R1) to giveimidazo[4,5-c]pyridines (C); b) introducing further substituents R², R⁴and/or R⁵≠H) either a) by cyclization of an appropriately substituted3,4-diaminopyridine (A) or b)) by introduction of the substituent(s)onto the imidazo[4,5]pyridine (C); c) reacting theimidazo[4,5c]pyridines (C) with an alkylating agent (D) (R³—X—R⁶) in anappropriate solvent under addition of a base at ambient temperature;optionally, in the case of hydroxy, mercapto or amino substituents inposition 4 or 6 of the imidazopyridine I(Z=O,S or NR); d) introductionof a further substituent (R²⁵ or R²⁶) at position 1 or 3 of theimidazo[4,5-c]pyridine.
 20. A method for preventing or treating a viralinfections in a subject or patient by administering to the patient inneed thereof a therapeutically effective amount of one or moreimidazo[4,5]pyridine derivatives according to formula (Z):

wherein: the dotted lines represent an optional double bond, providedthat no two double bonds are adjacent to one another, and that thedotted lines represent at least 3, optionally 4 double bonds; R¹ isselected from hydrogen; aryl unsubstituted or substituted with one ormore R⁶ heterocyclic ring unsubstituted or substituted with one or moreR⁶, C₃₋₁₀ cycloalkyl unsubstituted or substituted with one or more R⁶and C₄₋₁₀ cycloalkenyl unsubstituted or substituted with one or more R⁶;Y is selected from the group consisting of a single bond, O; S(O)_(m);NR¹¹; and a divalent, saturated or unsaturated, substituted orunsubstituted C₁-C₁₀ hydrocarbon group optionally including one or moreheteroatoms in the main chain, said heteroatoms being selected from thegroups consisting of O, S, and N; such as C₁₋₆ alkylene, C₂₋₆alkenylene, C₂₋₆ alkynylene, —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—,—S—(CH₂)₁₋₅—, —(C₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—,—(CH₂)₁₋₄—NR¹¹—(CH₂)₁₋₄— and C₃₋₁₀ cycloalkylidene; each R² and R⁴ isindependently selected from the group consisting of hydrogen C₁₋₁₈alkyl; C₂₋₈ alkyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio;halogen; OH;. CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH;aryl; aryloxy; arylthio; aryl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl;C₃₋₁₀ cycloalkyloxy; C₃₋₁₀ to cycloalkylthio; C₃₋₁₀ cycloalkenyl; C₃₋₁₀cycloalkynyl, 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring; or, when one of R²⁵ or R²⁶ is different fromhydrogen, either R² or R⁴ is selected from (═O), (═S), and (═N²⁷); X isselected from the group consisting of a divalent, saturated orunsaturated, substituted or unsubstituted C₁-C₁₀ hydrocarbon groupoptionally including one or more heteroatoms in the main chain (providedthat the heteroatom is not linked to N of the nucleus), said heteroatomsbeing selected from the group consisting of O, S, and N; such as C₁₋₆alkylene, (for example —CH₂—, —CH(CH₃)—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—,—CH₂—CH₂—CH₂—CH₂), —(CH₂)₂₋₄—O—(CH₂)₂₋₄—, 13 (CH₂)₂₋₄—S—(CH₂)₂₋₄—,—(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene (suchas —CH═CH—CH₂—), C₂₋₆ alkynylene; m is any integer from 0 to 2; R³ isselected from the group consisting of aryl; aryloxy; arylthio;aryl-NR¹⁰—; 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring; and each of said aryl, aryloxy, arylthio,aryl-NR¹⁰—, 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring is optionally substituted with one or more R¹⁷;C₃₋₁₀ cycloalkyl, oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenylwith the proviso that the double bond cannot be adjacent to a nitrogen;H with the proviso that if X is an alkylene, an alkenylene or analkynylene, then X comprises at least 5 carbon atoms; R⁵ isindependently selected from the group consisting of hydrogen; C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio;halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH;aryl; aryloxy; arylthio; arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀cycloalkyl; C₃₋₁₀ cycloalkyloxy C₃₋₁₀ cycloalkylthio C₃₋₁₀ cycloalkenyl;C₃₋₁₀ cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring; each R⁶ and R¹⁷ is independently selected fromthe group consisting of hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl C₂₋₁₈alkynyl; C₁₋₁₈ alkoxy, C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃;haloalkyl; C(═O)R¹⁸; C(═S)R¹⁸; SH; aryl; aryloxy; arylthio; arylalkyl;arylalkyloxy (optionally a oxybenzyl); arylalkylthio (optionally abenzylthio); 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring; C₁₋₁₈ hydroxyalkyl; and each of said aryl,aryloxy, arylthio, arylalkyl, arylalkyloxy (optionally a oxybenzyl),arylalkylthio (optionally a benzylthio), 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl isoptionally substituted with 1 or more R¹⁹; each R⁷ and R⁸ isindependently selected from the group consisting of H; C₁₋₁₈ alkyl;C₁₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6 memberedheterocyclic ring; C(═O)R¹²; C(—S)R¹² ; an amino acid residue linkedthrough a carboxyl group thereof; alternatively, R⁷ and R⁸, togetherwith the nitrogen to which they are attached, combine to form a 5-6membered heterocyclic ring; each R⁹ and R¹⁸ is independently selectedfrom the group consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl an aminoacid residue linked through an amino group thereof; each R¹⁰ and R¹¹ isindependently selected from the group the group consisting of H; C₁₋₁₈alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl;C(═O)R¹²; 5-6 membered heterocyclin ring; an amino acid residue linkedthrough a carboxyl group thereof; R¹² is independently selected from thegroup consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid residue liked through anamino group thereof; each R¹³ and R¹⁴ is independently selected from thegroup consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═S)R¹²; an amino acidresidue linked through a carboxyl group thereof; each R¹⁵ and R¹⁶ isindependently selected from the group consisting of H; C₁₋₁₈ alkyl;C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀cycloalkenyl; amino acid residue linked through a carboxyl groupthereof; R¹⁹ is independently selected from the group consisting of H;C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈alkoxy, preferably C₁₋₆ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl; C₄₋₁₀cycloalkenyl; C₄₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR²⁰OR²¹; OCF₃;haloalkyl; C(═O)R²²; C(═S)R²²; SH; C(═O)N(C₁₋₆ alkyl), N(H)S(O)(O)(C₁₋₆alkyl); aryl; aryloxy, arylthio; arylalkyl; and each of said aryl,aryloxy, arylthio, arylalkyl substituted with 1 or more halogens,particularly a phenyl substituted with 1-2 halogens; hydroxyalkyl; 5 or6 membered heterocyclic, oxyheterocyclic or thioheterocyclic ring eachunsubstituted or substituted with 1 or more halogens; each R²⁰ and R²¹is independently selected from the group consisting of H; C₁₋₁₈ alkyl,preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ ; alkynyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹², C(═S)R¹²; R²² is independentlyselected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₁₋₁₈ alkoxy; NR²³R²⁴ ;aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; each R²³ and R²⁴ isindependently selected from the group the group consisting of H; C₁₋₁₈alkyl, preferably C₂₋₃ alkyl, wherein C₂₋₃ alkyl taken together with Nof R²² can form a saturated heterocycle, which heterocycle is optionallysubstituted with OH or aryl or an amino acid residue; each R²⁵ or R²⁶are absent or selected from the group consisting of of H, C₁₋₁₈ alkyl,preferably C₁₋₄ alkyl; C₃₋₁₀ cycloalkyl, such as C₋₁₀ bicycloalkyl;C₃₋₁₀ cycloalkenyl; (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl; aryl, such as phenyl;5 or 6 membered heterocyclic ring, such as pyridyl; alkylaryl such asbenzyl; and each of said C₁₋₁₈ alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀cycloalkyl, C₃₋₁₀ cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl, C₅₋₁₀bicycloalkyl adamantyl, phenyl, pyridyl and benzyl is optionallysubstituted with 1-4 of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OHoxybenzyl, and OH; and heterocyclic ring having 3 to 7 carbon atoms,preferably a saturated heterocyclic ring wherein the heteroatoms are S,S(O), or S(O)₂ separated from the imidazopyridyl ring nitrogen atom byat least 2 heterocyclic ring carbon atoms. Provided that either R²⁵ orR²⁶ is hydrogen Typically R²⁵ or R²⁶ is cyclopentyl or cyclohexyl;provided that if the compound is substituted at R²⁵ or R²⁶, either R² orR⁴ is selected from (═O), (═S), and (═NR²⁷); and R²⁷ is selected fromthe group consisting of H C₁₋₁₈ alkyls C₃₋₁₀ cycloalkyl, (C₃₋₁₀cycloalkyl)-C₁₋₆ alkyl; aryl; arylalkyl, such as benzyl; as an activeingredient, optionally in a mixture with at least a pharmaceuticallyacceptable carrier.
 21. A method of screening antiviral compounds whichcomprises a) providing a compounds of the formula (Z)

wherein: the dotted lines represent an optional double bond, providedthat no two double bonds are adjacent to one another, and that thedotted lies represent at least 3, optionally 4 double bonds; R¹ isselected from hydrogen; aryl unsubstituted or substituted with one ormore R⁶, heterocyclic ring unsubstituted or substituted with one or moreR⁶, C₃₋₁₀ cycloalkyl unsubstituted or substituted with one or more R⁶and C₄₋₁₀ cycloalkenyl unsubstituted or substituted with one or more R⁶;Y is selected from the group consisting of a single bond O; S(O)_(m);NR¹¹; and a divalent, saturated or unsaturated, substituted orunsubstituted C₁-C₁₀ hydrocarbon group optionally including one or moreheteroatoms in the main claim, said heteroatoms being selected from thegroups consisting of O, S, and N; such as C₁₋₆ alkylene, C₂₋₆alkenylene,C₂₋₆ alkynylene, —O(CH₂)₁₋₅—, —(CH₂)₁₋₄—O—(CH₂)₁₋₄—, —S—(CH₂)₁₋₅—,—(CH₂)₁₋₄—S—(CH₂)₁₋₄—, —NR¹¹—(CH₂)₁₋₅—, —(CH₂)₁₋₄—N¹¹—(CH₂)₁₋₄ and C₃₋₁₀cycloalkylidene; each R² and R⁴ is independently selected from the groupconsisting of hydrogen C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈alkoxy, C₁₋₁₈ alkylthio; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃; haloalkyl;C(═O)R⁹; C(═S)R⁹; SH; aryl; aryloxy; arylthio; arylalkyl; C₁₋₁₈hydroxyalkyl; C₃₋₁₀ to cycloalkyl; C₃₋₁₀ cycloalkyloxy; C₃₋₁₀cycloalkylthio; C₃₋₁₀ cycloalkenyl; C₃₋₁₀ cycloalkynyl; 5 or 6 memberedheterocyclic, oxyheterocyclic or thioheterocyclic ring; or, when one ofR²⁵ or R²⁵ is different from hydrogen either R² or R⁴ is selected from(═O), (═S), and (═NR²⁷); X is selected from the group consisting of adivalent, saturated or unsaturated, substituted or unsubstituted C₁-C₁₀hydrocarbon group optionally including one or more heteroatoms in themain chain (provided that the heteroatom is not linked to N of thenucleus), said heteroatoms being selected from the group consisting ofO, S, and N; such as C₁₋₆ alkylene, (for example —CH₂—, —CH(CH₃)—,—CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂), —(CH₂)₂₋₄—O—(CH₂)₂₋₄—,—(CH₂)₂₋₄—NR¹⁰—(CH₂)₂₋₄—, C₃₋₁₀ cycloalkylidene, C₂₋₆ alkenylene (suchas —CH═CH—CH₂—), C₂₋₆ alkynylene; m is any integer from 0 to 2; R³ isselected from the group consisting of aryl; aryloxy; arylthio;aryl-NR¹⁰—; 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring; and each of said aryl, aryloxy, arylthio,aryl-NR¹⁰—, 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring is optionally substituted with one or More R¹⁷;C₃₋₁₀ cycloalkyl, oxycycloalkyl or thiocycloalkyl; C₄₋₁₀ cycloalkenylwith the proviso that the double bond cannot be adjacent to a nitrogen;H with the proviso that if X is an alkylene, an alkenylene or analkynylene, then X comprises at least 5 carbon atoms; R⁵ isindependently selected from the group consisting of hydrogen; C₁₋₁₈alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio;halogen; OH; CN; NO₂; NR⁷R⁸; CF₃; haloalkyl; C(═O)R⁹; C(═S)R⁹; SH; aryl;aryloxy; arylthio; arylalkyl; C₁₋₁₈ hydroxyalkyl; C₃₋₁₀ cycloalkyl;C₃₋₁₀ cycloalkyloxy; C3.10 cycloalkylthio C₃₋₁₀ cycloalkenyl; C₃₋₁₀cycloalkynyl; 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring; each R⁶ and R¹⁷ is independently selected fromthe group consisting of hydrogen; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈aryl; C₁₋₁₈ alkoxy; C₁₋₁₈ alkylthio; C₃₋₁₀ cycloalkyl, C₃₋₁₀cycloalkenyl or C₃₋₁₀ cycloalkynyl; halogen; OH; CN; NO₂; NR⁷R⁸; OCF₃,haloalkyl; C(═O)R¹⁸; C(═S)R¹⁸; SH; aryl; aryloxy; arylthio; arylalkyl;arylalkyloxy (optionally a oxybenzyl); arylalkylthio (optionally abenzylthio); 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring, C₁₋₁₈ hydroxyalkyl; and each of said aryl,aryloxy, arylthio, arylalkyl, arylalkyloxy (optionally a oxybenzyl),arylalkylthio (optionally a benzylthio), 5 or 6 membered heterocyclic,oxyheterocyclic or thioheterocyclic ring, C₁₋₁₈ hydroxyalkyl isoptionally substituted with 1 or more R¹⁹; each R⁷ and R⁸ isindependently selected from the group consisting of H; C₁₋₁₈ alkyl;C₁₋₁₈ alkenyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; 5-6 memberedheterocyclic ring; C(═O)R¹²; C(═S)R¹²; an amino acid residue linkedthrough a carboxyl group thereof; alternatively, R⁷ and R⁸, togetherwith the nitrogen to which they are attached, combine to form a 5-6membered heterocyclic ring; each R⁹ and R¹⁸ is independently selectedfrom the group consisting of H; OH; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; C₁₋₁₈ alkoxy; NR¹⁵R¹⁶; aryl an aminoacid residue linked through an amino group thereof; each R¹⁰ and R¹¹ isindependently selected from the group the group consisting of H; C₁₋₁₈alkyl; C₁₋₁₈ alkenyl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; aryl;C(═O)R¹²; 5-6 membered heterocyclin ring, an amino acid residue linkedthrough a carboxyl group thereof; R¹² is independently selected from thegroup consisting of H; C₁₋₁₈ alkyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; an amino acid residue linked through anamino group thereof; each R¹³ and R¹⁴ is independently selected from thegroup consisting of H; C₁₋₁₈ allyl; C₂₋₁₈ alkenyl; aryl; C₃₋₁₀cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²; C(═)R¹²; an amino acid residuelinked through a carboxyl group thereof; each R¹⁵ and R¹⁶ isindependently selected from the group consisting of H; C₁₋₁₈ alkyl;C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀cycloalkenyl; an amino acid residue linked through a carboxyl groupthereof, R¹⁹ is independently selected from the group consisting of H;C₁₋₁₈ alkyl preferably C₁₋₆ alkyl; C₂₋₁₈ alkenyl; C₂₋₁₈ alkynyl; C₁₋₁₈alkoxy, preferably C₁₋₆alkoxy, C₁₋₁₈ alkylthio; C₃ cycloalkyl; C₄₋₁₀cycloalkenyl; C₄₋₁₀ to cycloalkynyl; halogen; OH; CN; NO₂; NR²⁶R²¹;OCF₃; haloalkyl; C(═O)R²²; C(═S)R²³; SH; C(═O)N(C₁₋₆ alkyl),N(H)S(O)(O)(C₁₋₆ alkyl); aryl; aryloxy; arylthio; arylalkyl; and each ofsaid aryl, aryloxy, arylthio, arylalkyl substituted with 1 or morehalogens, particularly a phenyl substituted with 1-2 halogens;hydroxyalkyl; 5 or 6 membered heterocyclic, oxyheterocyclic orthioheterocyclic ring each unsubstituted or substituted with 1 or morehalogens; each R²⁰ and R²¹ is independently selected from the groupconsisting of H; C₁₋₁₈ alkyl, preferably C₁₋₆ alkyl; C₂₋₁₈ s alkenyl;C₂₋₁₈ alkynyl; aryl; C₃₋₁₀ cycloalkyl; C₄₋₁₀ cycloalkenyl; C(═O)R¹²,C(═S)R¹²; R²² is independently selected from H; OH; C₁₋₁₈ alkyl; C₂₋₁₈alkenyl; C₁₋₁₈ alkoxy, NR²³R²⁴; aryl; C₃₋₁₀ to cycloalkyl,; C₄₋₁₀cycloalkynyl; Each R²³ and R²⁴ is independently selected from the groupthe group consisting of H; C₁₋₁₈ alkyl, preferably C₂₋₃ alkyl, whereinC₂₋₃ alkyl taken together with N of R²² can form a saturatedheterocycle, which heterocycle is optionally substituted with OH or arylor an amino acid residue; each R²⁵ or R²⁶ are absent or selected fromthe group consisting of of H, C₁₋₁₈ alkyl, preferably C₁₋₄ alkyl; C₃₋₁₀cycloalkyl, such as C₅₋₁₀ bicycloalkyl; C₃₋₁₀ cycloalkenyl; (C₃₋₁₀cycloalkyl)-C₁₋₃ alkyl; aryl, such as phenyl; 5 or 6 memberedheterocyclic ring, such as pyridyl; alkylaryl, such as benzyl; and eachof said C₁₋₁₈ alkyl, preferably C₁₋₄ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₁₀cycloalkenyl, (C₃₋₈ cycloalkyl)-C₁₋₃ alkyl C₁₋₁₀ bicycloalkyl,adamantyl, phenyl, pyridyl and benzyl is optionally substituted with 1-4of each of C₁₋₆ alkyl, C₁₋₆ alkoxy, halo, CH₂OH, oxybenzyl, and OH; andheterocyclic ring having 3 to 7 carbon atoms, preferably a saturatedheterocyclic ring wherein the heteroatoms are S, S(O), or S(O)₂separated from the imidazopyridyl ring nitrogen atom by at least 2heterocyclic ring carbon atoms. Provided that either R²⁵ or R²⁶ ishydrogen. Typically R²⁵ or R²⁶ is cyclopentyl or cyclohexyl; providedthat if the compound is substituted at R²⁵ or R²⁶, either R² or R⁴ isselected from (═O), (═S), and (═NR²⁷); and R²⁷ is selected from thegroup consisting of H, C₁₋₁₈ alkoxy, C₃₋₁₀ cycloalkyl, (C₃₋₁₀cycloalkyl)-C₁₋₆ alkyl; aryl; arylalkyl such as benzyl; and b)determining the anti-viral activity of said compound.
 22. The method ofclaim 21, wherein said antiviral activity is determined by the activityof said compound against one or more viruses belonging to the family ofthe Flaviviridae and/or of the Picornaviridae.